B F Cravatt

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. ncbi request reprint Chemical strategies for the global analysis of protein function
    B F Cravatt
    The Skaggs Institute for Chemical Biology and the Departments of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Chem Biol 4:663-8. 2000
  2. ncbi request reprint The enzymatic inactivation of the fatty acid amide class of signaling lipids
    Benjamin F Cravatt
    Departments of Cell Biology and Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Phys Lipids 121:135-48. 2002
  3. doi request reprint Enzyme inhibitor discovery by activity-based protein profiling
    Micah J Niphakis
    The Skaggs Institute for Chemical Biology and the Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037 email
    Annu Rev Biochem 83:341-77. 2014
  4. pmc Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
    Jonathan Z Long
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 5:37-44. 2009
  5. pmc DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses
    Ku Lung Hsu
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 8:999-1007. 2012
  6. pmc Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice
    Silvia Ortega-Gutierrez
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California, United States of America
    PLoS ONE 3:e2486. 2008
  7. pmc NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink
    Olesya A Ulanovskaya
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 9:300-6. 2013
  8. pmc Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells
    Jonathan J Hulce
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA
    Nat Methods 10:259-64. 2013
  9. pmc Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes
    Daniel A Bachovchin
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA
    Nat Biotechnol 27:387-94. 2009
  10. pmc Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids
    Jonathan Z Long
    The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 7:763-5. 2011

Research Grants

Detail Information

Publications120 found, 100 shown here

  1. ncbi request reprint Chemical strategies for the global analysis of protein function
    B F Cravatt
    The Skaggs Institute for Chemical Biology and the Departments of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Chem Biol 4:663-8. 2000
    ..Of particular interest is a new breed of strategies that employs synthetic chemistry to enrich our understanding of protein function on a global scale...
  2. ncbi request reprint The enzymatic inactivation of the fatty acid amide class of signaling lipids
    Benjamin F Cravatt
    Departments of Cell Biology and Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Phys Lipids 121:135-48. 2002
    ....
  3. doi request reprint Enzyme inhibitor discovery by activity-based protein profiling
    Micah J Niphakis
    The Skaggs Institute for Chemical Biology and the Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037 email
    Annu Rev Biochem 83:341-77. 2014
    ..These studies demonstrate the value of selective chemical probes as drivers of biological inquiry. ..
  4. pmc Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
    Jonathan Z Long
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 5:37-44. 2009
    ..These data indicate that 2-AG endogenously modulates several behavioral processes classically associated with the pharmacology of cannabinoids and point to overlapping and unique functions for 2-AG and anandamide in vivo...
  5. pmc DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses
    Ku Lung Hsu
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 8:999-1007. 2012
    ..These findings indicate that DAGLβ is a key metabolic hub within a lipid network that regulates proinflammatory responses in macrophages...
  6. pmc Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice
    Silvia Ortega-Gutierrez
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California, United States of America
    PLoS ONE 3:e2486. 2008
    ..Methylesterification is thought to control the binding of different B subunits to AC dimers, but little is known about its physiological significance in vivo...
  7. pmc NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink
    Olesya A Ulanovskaya
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 9:300-6. 2013
    ..Our findings thus point to a direct mechanistic link between the deregulation of a metabolic enzyme and widespread changes in the methylation landscape of cancer cells...
  8. pmc Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells
    Jonathan J Hulce
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA
    Nat Methods 10:259-64. 2013
    ....
  9. pmc Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes
    Daniel A Bachovchin
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA
    Nat Biotechnol 27:387-94. 2009
    ..Furthermore, we show that the detoxification enzyme GSTO1, also implicated in cancer, is inhibited by several electrophilic compounds found in public libraries, some of which display high selectivity for this protein...
  10. pmc Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids
    Jonathan Z Long
    The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 7:763-5. 2011
    ..Abhd3(-/-) mice possess elevated myristoyl (C14)-phospholipids, including the bioactive lipid C14-lysophosphatidylcholine, confirming the physiological relevance of our substrate assignments...
  11. pmc Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system
    Joel E Schlosburg
    Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA
    Nat Neurosci 13:1113-9. 2010
    ..Thus, individual endocannabinoids generate distinct analgesic profiles that are either sustained or transitory and associated with agonism and functional antagonism of the brain cannabinoid system, respectively...
  12. pmc Click-generated triazole ureas as ultrapotent in vivo-active serine hydrolase inhibitors
    Alexander Adibekian
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Nat Chem Biol 7:469-78. 2011
    ..These data indicate 1,2,3-triazole ureas are a pharmacologically privileged chemotype for serine hydrolase inhibition, combining broad activity across the serine hydrolase class with tunable selectivity for individual enzymes...
  13. pmc Quantitative reactivity profiling predicts functional cysteines in proteomes
    Eranthie Weerapana
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nature 468:790-5. 2010
    ....
  14. pmc The endocannabinoid anandamide is a precursor for the signaling lipid N-arachidonoyl glycine by two distinct pathways
    Heather B Bradshaw
    The Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
    BMC Biochem 10:14. 2009
    ..Here using both in vitro and in vivo assays measuring metabolites with LC/MS/MS we test the hypothesis that both pathways are present in mammalian cells...
  15. pmc Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis
    Jennifer M Milner
    Musculoskeletal Research Group, Newcastle University, Newcastle upon Tyne, UK
    Arthritis Res Ther 8:R23. 2006
    ..Its cell surface location and expression profile suggest that it may have an important pathological role in the cartilage turnover prevalent in arthritic diseases...
  16. pmc Functional disassociation of the central and peripheral fatty acid amide signaling systems
    Benjamin F Cravatt
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:10821-6. 2004
    ..These data suggest that the central and peripheral FAA signaling systems regulate discrete behavioral processes and may be targeted for distinct therapeutic gain...
  17. ncbi request reprint Fatty acid amide hydrolase: an emerging therapeutic target in the endocannabinoid system
    Benjamin F Cravatt
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Chem Biol 7:469-75. 2003
    ....
  18. ncbi request reprint The endogenous cannabinoid system and its role in nociceptive behavior
    Benjamin F Cravatt
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, California 92037, USA
    J Neurobiol 61:149-60. 2004
    ..Collectively, these investigations support a role for endocannabinoids in modulating behavioral responses to acute, inflammatory, and neuropathic pain stimuli...
  19. pmc Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase
    B F Cravatt
    The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 98:9371-6. 2001
    ..FAAH may therefore represent an attractive pharmaceutical target for the treatment of pain and neuropsychiatric disorders...
  20. doi request reprint Activity-based protein profiling: from enzyme chemistry to proteomic chemistry
    Benjamin F Cravatt
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Annu Rev Biochem 77:383-414. 2008
    ..Here, we review the basic technology of ABPP, the enzyme classes addressable by this method, and the biological discoveries attributable to its application...
  21. ncbi request reprint The biological impact of mass-spectrometry-based proteomics
    Benjamin F Cravatt
    Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 450:991-1000. 2007
    ....
  22. pmc Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamide
    D L Boger
    Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 97:5044-9. 2000
    ....
  23. pmc Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain
    S G Kinsey
    Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia, USA
    J Pharmacol Exp Ther 330:902-10. 2009
    ..These data indicate that inhibition of FAAH and MAGL reduces neuropathic pain through distinct receptor mechanisms of action and present viable targets for the development of analgesic therapeutics...
  24. ncbi request reprint Characterization and manipulation of the acyl chain selectivity of fatty acid amide hydrolase
    M P Patricelli
    The Department of Cell Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 40:6107-15. 2001
    ....
  25. pmc Chemical requirements for inhibition of gap junction communication by the biologically active lipid oleamide
    D L Boger
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 95:4810-5. 1998
    ..A select set of agents has been identified that serves both as oleamide agonists and as inhibitors of fatty acid amide hydrolase, which is responsible for the rapid inactivation of oleamide...
  26. ncbi request reprint Comparative characterization of a wild type and transmembrane domain-deleted fatty acid amide hydrolase: identification of the transmembrane domain as a site for oligomerization
    M P Patricelli
    Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Biochemistry 37:15177-87. 1998
    ..Self-association through FAAH's transmembrane domain was further demonstrated by a FAAH transmembrane domain-GST fusion protein which formed SDS-resistant dimers and large oligomeric assemblies in solution...
  27. ncbi request reprint Fatty acid amide hydrolase, the degradative enzyme for anandamide and oleamide, has selective distribution in neurons within the rat central nervous system
    E A Thomas
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Neurosci Res 50:1047-52. 1997
    ..The FAAH distribution in the CNS suggests that degradation of neuromodulatory fatty acid amides at their sites of action influences their effects on sleep, euphoria, and analgesia...
  28. pmc Molecular characterization of human and mouse fatty acid amide hydrolases
    D K Giang
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 94:2238-42. 1997
    ..The identification of highly homologous FAAH proteins in rat, mouse, and human supports a general role for the fatty acid amides in mammalian biology...
  29. pmc Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase
    F Anthony Romero
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 50:1058-68. 2007
    ..Proteomic-wide screening of the inhibitors revealed that most are exquisitely selective for FAAH over all other mammalian proteases, reversing the 100-fold preference of 20a (C5 substituent = H) for the enzyme TGH...
  30. ncbi request reprint Fatty acid amide hydrolase substrate specificity
    D L Boger
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 10:2613-6. 2000
    ..FAAH hydrolyzes a range of fatty acid amides, and the present study examines the relative rates of hydrolysis of a variety of natural and unnatural fatty acid primary amide substrates using pure recombinant rat FAAH...
  31. ncbi request reprint An endogenous sleep-inducing compound is a novel competitive inhibitor of fatty acid amide hydrolase
    M P Patricelli
    Skaggs Institute for Chemical Biology, La Jolla, California, USA
    Bioorg Med Chem Lett 8:613-8. 1998
    ..Additionally, the characterization of gamma-halo beta-keto esters as powerful FAAH inhibitors near physiological pH may aid in future studies of the enzymology and biological properties of FAAH...
  32. ncbi request reprint Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules
    D L Boger
    Department of Chemistry, Scripps Research Institute, La Jolla, California 92037, USA
    Curr Pharm Des 4:303-14. 1998
    ..Oleamide has been shown to modulate serotonergic neurotransmission and inhibit intercellular gap junction communication and detailed studies of its well defined and selective structural features required for activity have been disclosed...
  33. ncbi request reprint Proteins regulating the biosynthesis and inactivation of neuromodulatory fatty acid amides
    M P Patricelli
    Skaggs Institute for Chemical Biology and the Department of Cell Biology, Scripps Research Institute, La Jolla, California, USA
    Vitam Horm 62:95-131. 2001
    ....
  34. ncbi request reprint Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use
    Kyle P Chiang
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Hum Mol Genet 13:2113-9. 2004
    ....
  35. pmc A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol
    Jacqueline L Blankman
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Biol 14:1347-56. 2007
    ..Interestingly, MAGL, ABHD6, and ABHD12 display distinct subcellular distributions, suggesting that they may control different pools of 2-AG in the nervous system...
  36. ncbi request reprint A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases
    Weiwei Li
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 129:9594-5. 2007
  37. ncbi request reprint Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity
    Donmienne Leung
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 15:1423-8. 2005
    ....
  38. ncbi request reprint Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
    B F Cravatt
    Department of Chemistry, The Scripps Research Institute, La Jolla, California 92307, USA
    Nature 384:83-7. 1996
    ..Therefore we will hereafter refer to oleamide hydrolase as fatty-acid amide hydrolase, in recognition of the plurality of fatty-acid amides that the enzyme can accept as substrates...
  39. ncbi request reprint A second mammalian N-myristoyltransferase
    D K Giang
    Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 273:6595-8. 1998
    ....
  40. ncbi request reprint Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizations
    K Kustedjo
    Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 275:27933-9. 2000
    ..The potential relationship between the altered subcellular distribution of DeltaE-torsin A and the disease-inducing phenotype of the protein is discussed...
  41. ncbi request reprint Profiling the specific reactivity of the proteome with non-directed activity-based probes
    G C Adam
    The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA
    Chem Biol 8:81-95. 2001
    ....
  42. ncbi request reprint Characterization of the sleep-wake patterns in mice lacking fatty acid amide hydrolase
    Salvador Huitron-Resendiz
    Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA
    Sleep 27:857-65. 2004
    ..To determine if, in the absence of FAAH, the hypnogenic fatty acid amides induce an increase of sleep, we characterized the sleep-wake patters in FAAH-knockout mice [FAAH (-/-)] before and after sleep deprivation...
  43. pmc Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case study
    Gabriel M Simon
    Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 285:11051-5. 2010
    ....
  44. ncbi request reprint Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase
    Angela B Clement
    The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    J Neurosci 23:3916-23. 2003
    ..More generally, these findings demonstrate that the disinhibitory actions of endocannabinoids observed in hippocampal slices in vitro may also occur in vivo...
  45. ncbi request reprint Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling
    Michael H Bracey
    Department of Cell Biology, Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 298:1793-6. 2002
    ....
  46. ncbi request reprint A second fatty acid amide hydrolase with variable distribution among placental mammals
    Binqing Q Wei
    The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 281:36569-78. 2006
    ..The apparent loss of the FAAH-2 gene in some lower mammals should be taken into consideration when extrapolating genetic or pharmacological findings on the fatty acid amide signaling system across species...
  47. pmc Correlation of inhibitor effects on enzyme activity and thermal stability for the integral membrane protein fatty acid amide hydrolase
    Ian M Slaymaker
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 18:5847-50. 2008
    ....
  48. ncbi request reprint Discovering potent and selective reversible inhibitors of enzymes in complex proteomes
    Donmienne Leung
    The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nat Biotechnol 21:687-91. 2003
    ..In this way, promiscuous inhibitors were readily rejected in favor of equally potent compounds with 500-fold or greater selectivity for their targets...
  49. pmc X-ray crystallographic analysis of alpha-ketoheterocycle inhibitors bound to a humanized variant of fatty acid amide hydrolase
    Mauro Mileni
    Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 53:230-40. 2010
    ..The detailed analysis of their key active site interactions and their implications on the interpretation of the available structure-activity relationships are discussed providing important insights for future design...
  50. ncbi request reprint Chemical characterization of a family of brain lipids that induce sleep
    B F Cravatt
    Department of Chemistry, Scripps Research Institute, La Jolla, CA 92307, USA
    Science 268:1506-9. 1995
    ..Synthetic cis-9,10-octadecenoamide induced physiological sleep when injected into rats. Together, these results suggest that fatty acid primary amides may represent a previously unrecognized class of biological signaling molecules...
  51. ncbi request reprint Profiling serine hydrolase activities in complex proteomes
    D Kidd
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Biochemistry 40:4005-15. 2001
    ..Collectively, these studies demonstrate that chemical probes such as the biotinylated FPs can greatly accelerate both the functional characterization and molecular identification of active enzymes in complex proteomes...
  52. ncbi request reprint Endocannabinoid biosynthesis proceeding through glycerophospho-N-acyl ethanolamine and a role for alpha/beta-hydrolase 4 in this pathway
    Gabriel M Simon
    Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 281:26465-72. 2006
    ..These results support the existence of an NAPE-PLD-independent route for NAE biosynthesis and suggest that Abh4 plays a role in this metabolic pathway by acting as a (lyso)NAPE-selective lipase...
  53. ncbi request reprint Activity-based protein profiling in vivo using a copper(i)-catalyzed azide-alkyne [3 + 2] cycloaddition
    Anna E Speers
    The Skaggs Institute for Chemical Biology, Departments of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 125:4686-7. 2003
    ..This click chemistry-based strategy for ABPP represents a unique and versatile method for functional proteome analysis...
  54. ncbi request reprint The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolases
    Jessica P Alexander
    Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 128:9699-704. 2006
    ..More generally, the proteome-wide target promiscuity of LY2183240 designates the heterocyclic urea as a chemotype with potentially excessive protein reactivity for drug design...
  55. ncbi request reprint A FAAH-regulated class of N-acyl taurines that activates TRP ion channels
    Alan Saghatelian
    Department of Cell Biology, The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 45:9007-15. 2006
    ....
  56. pmc Ligands in crystal structures that aid in functional characterization
    Anna E Speers
    The Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 66:1306-8. 2010
    ..This introduction provides an overview and commentary on the value of liganded structures emerging from the JCSG structural genomics initiative...
  57. pmc Structure-guided inhibitor design for human FAAH by interspecies active site conversion
    Mauro Mileni
    The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 105:12820-4. 2008
    ..This structure offers compelling insights to explain the species selectivity of FAAH inhibitors, which should guide future drug design programs...
  58. pmc Exploration of a fundamental substituent effect of alpha-ketoheterocycle enzyme inhibitors: Potent and selective inhibitors of fatty acid amide hydrolase
    Jessica K DeMartino
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 18:5842-6. 2008
    ..90) with a slope of 3.37 (rho=3.37), that is of a magnitude that indicates that of the electron-withdrawing character of the substituent dominates its effects (a one unit change in sigma(m) provides a >1000-fold change in K(i))...
  59. pmc A missense mutation in human fatty acid amide hydrolase associated with problem drug use
    Jack C Sipe
    Departments of Molecular and Experimental Medicine, Chemistry, and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:8394-9. 2002
    ....
  60. pmc Disparate proteome reactivity profiles of carbon electrophiles
    Eranthie Weerapana
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 4:405-7. 2008
    ..These data specify electrophilic chemotypes with restricted and permissive reactivity profiles to guide the design of next-generation functional proteomics probes...
  61. ncbi request reprint Chemical strategies for activity-based proteomics
    Anna E Speers
    The Skaggs Institute for Chemical Biology, Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Chembiochem 5:41-7. 2004
    ..These strategies for activity-based protein profiling enable both the discovery and functional analysis of enzymes associated with human disease...
  62. ncbi request reprint Structure and function of fatty acid amide hydrolase
    Michele K McKinney
    Departments of Cell Biology and Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Annu Rev Biochem 74:411-32. 2005
    ..These studies, as well as their biological and therapeutic implications, are the subject of this review...
  63. pmc Biomarkers of endocannabinoid system activation in severe obesity
    Jack C Sipe
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America
    PLoS ONE 5:e8792. 2010
    ....
  64. pmc Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics
    Dale L Boger
    Department of Chemistry, Cell Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 48:1849-56. 2005
    ....
  65. pmc Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo
    Jonathan Z Long
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:20270-5. 2009
    ....
  66. pmc Mechanism of carbamate inactivation of FAAH: implications for the design of covalent inhibitors and in vivo functional probes for enzymes
    Jessica P Alexander
    The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Chem Biol 12:1179-87. 2005
    ..The experimental strategy described herein can be used to create in vivo probes for any enzyme susceptible to covalent inhibition...
  67. ncbi request reprint Assignment of endogenous substrates to enzymes by global metabolite profiling
    Alan Saghatelian
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 43:14332-9. 2004
    ..Thus, global metabolite profiling establishes unanticipated connections between the proteome and metabolome that enable assignment of an enzyme's unique biochemical functions in vivo...
  68. ncbi request reprint Conserved chromosomal location and genomic structure of human and mouse fatty-acid amide hydrolase genes and evaluation of clasper as a candidate neurological mutation
    M Wan
    Department of Genetics, Stanford University School of Medicine, Stanford, California, 94305, USA
    Genomics 54:408-14. 1998
    ..FAAH protein levels were normal in clasper mouse tissues as determined by enzyme activity assays and Western blotting...
  69. ncbi request reprint Structural basis for a disfavored elimination reaction in catalytic antibody 1D4
    N A Larsen
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    J Mol Biol 314:93-102. 2001
    ..1D4 has pushed the boundaries of antibody-mediated catalysis into the realm of disfavored reactions and, hence, represents an important milestone in the development of this technology...
  70. ncbi request reprint Effect of oleamide on sleep and its relationship to blood pressure, body temperature, and locomotor activity in rats
    S Huitron-Resendiz
    Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA
    Exp Neurol 172:235-43. 2001
    ..These latter effects were not correlated in time with the observed increases in slow-wave sleep. These data suggest that the hypnogenic effects of oleamide are not related to changes in blood pressure, heart rate, or body temperature...
  71. ncbi request reprint Mechanistic and structural requirements for active site labeling of phosphoglycerate mutase by spiroepoxides
    Michael J Evans
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Mol Biosyst 3:495-506. 2007
    ..More generally, our findings provide further evidence that useful pharmacological tools can emerge from screening structurally diverse libraries of protein-reactive probes...
  72. pmc Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolase
    Christophe Hardouin
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Med Chem 50:3359-68. 2007
    ..Proteome-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases...
  73. ncbi request reprint Mapping enzyme active sites in complex proteomes
    Gregory C Adam
    The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 126:1363-8. 2004
    ....
  74. ncbi request reprint Trifunctional chemical probes for the consolidated detection and identification of enzyme activities from complex proteomes
    Gregory C Adam
    The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Mol Cell Proteomics 1:828-35. 2002
    ....
  75. ncbi request reprint Structure-based design of a FAAH variant that discriminates between the N-acyl ethanolamine and taurine families of signaling lipids
    Michele K McKinney
    Department of Cell Biology, The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 45:9016-22. 2006
    ..The G268D FAAH mutant may thus serve as a valuable research tool to illuminate the unique roles played by the NAE and NAT classes of signaling lipids in vivo...
  76. ncbi request reprint Discovery metabolite profiling--forging functional connections between the proteome and metabolome
    Alan Saghatelian
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, United States
    Life Sci 77:1759-66. 2005
    ..These findings show that DMP can establish direct connections between the proteome and metabolome and thus offers a powerful strategy to assign physiological functions to enzymes in the post-genomic era...
  77. ncbi request reprint Chemical strategies for functional proteomics
    Gregory C Adam
    The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Mol Cell Proteomics 1:781-90. 2002
    ..Additionally, we discuss the emerging field of activity-based protein profiling, which aims to synthesize and apply small molecule probes that monitor dynamics in protein function in complex proteomes...
  78. ncbi request reprint Endocannabinoid metabolism in the absence of fatty acid amide hydrolase (FAAH): discovery of phosphorylcholine derivatives of N-acyl ethanolamines
    Anke M Mulder
    Department of Cell Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 45:11267-77. 2006
    ..These data indicate the presence of a complete metabolic pathway for the production and degradation of PC-NAEs in the CNS that constitutes an alternative route for endocannabinoid metabolism...
  79. ncbi request reprint Mechanism-based profiling of enzyme families
    Michael J Evans
    The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
    Chem Rev 106:3279-301. 2006
  80. ncbi request reprint Profiling enzyme activities in vivo using click chemistry methods
    Anna E Speers
    The Skaggs Institute for Chemical Biology, Departments of Chemistry and Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Biol 11:535-46. 2004
    ....
  81. pmc Binding and inactivation mechanism of a humanized fatty acid amide hydrolase by alpha-ketoheterocycle inhibitors revealed from cocrystal structures
    Mauro Mileni
    Departments of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:10497-506. 2009
    ....
  82. ncbi request reprint Comparison of anandamide transport in FAAH wild-type and knockout neurons: evidence for contributions by both FAAH and the CB1 receptor to anandamide uptake
    Silvia Ortega-Gutierrez
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Biochemistry 43:8184-90. 2004
    ....
  83. doi request reprint Optimization of activity-based probes for proteomic profiling of histone deacetylase complexes
    Cleo M Salisbury
    The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 130:2184-94. 2008
    ....
  84. pmc Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profiling
    Heather S Hoover
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 18:5838-41. 2008
    ..Interestingly, a minimal overlap in target profiles was observed for THL and RHC80267, suggesting that pharmacological effects observed with both agents may be viewed as good initial evidence for DAGL-dependent events...
  85. pmc Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study
    Ryuichiro Nakai
    Department of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem 17:1101-8. 2009
    ..We anticipate that ABPP will find general utility as a platform to rank the selectivity of lead compounds emerging from HTS assays for a wide variety of enzymes...
  86. pmc Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolism
    Jonathan Z Long
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Rd La Jolla, CA 92037, USA
    Chem Biol 16:744-53. 2009
    ..Collectively, these studies indicate that MAGL exerts tissue-dependent control over endocannabinoid and monoglyceride metabolism and designate JZL184 as a selective tool to characterize the functions of MAGL in vivo...
  87. pmc Proteomic profiling of metalloprotease activities with cocktails of active-site probes
    Stephan A Sieber
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 2:274-81. 2006
    ..These findings suggest that chemical proteomic methods can serve as a universal strategy to profile the activity of the metalloprotease superfamily in complex biological systems...
  88. ncbi request reprint Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling
    Michael J Evans
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Biotechnol 23:1303-7. 2005
    ..More generally, the incorporation of protein-reactive compounds into chemical genomics screens offers a means to discover targets of bioactive small molecules in living systems, thereby enabling downstream mechanistic investigations...
  89. ncbi request reprint Class assignment of sequence-unrelated members of enzyme superfamilies by activity-based protein profiling
    Nadim Jessani
    Skaggs Institute for Chemical Biology and Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 44:2400-3. 2005
  90. ncbi request reprint Discovering disease-associated enzymes by proteome reactivity profiling
    Katherine T Barglow
    The Skaggs Institute for Chemical Biology and Department of Cell Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Chem Biol 11:1523-31. 2004
    ....
  91. ncbi request reprint Assignment of protein function in the postgenomic era
    Alan Saghatelian
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 1:130-42. 2005
    ..Here, we highlight a new breed of 'postgenomic' methods that aim to assign functions to proteins through the integrated application of chemical and biological techniques...
  92. ncbi request reprint Evidence for distinct roles in catalysis for residues of the serine-serine-lysine catalytic triad of fatty acid amide hydrolase
    Michele K McKinney
    Department of Cell Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:37393-9. 2003
    ....
  93. pmc Maternal PPAR gamma protects nursing neonates by suppressing the production of inflammatory milk
    Yihong Wan
    Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Genes Dev 21:1895-908. 2007
    ..Therefore, maternal PPAR gamma is pivotal for maintaining the quality of milk and protecting the nursing newborns by suppressing the production of inflammatory lipids in the lactating mammary gland...
  94. pmc Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness
    Nadim Jessani
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:10335-40. 2002
    ....
  95. pmc Chemical proteomic probes for profiling cytochrome p450 activities and drug interactions in vivo
    Aaron T Wright
    The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Biol 14:1043-51. 2007
    ....
  96. ncbi request reprint Proteomic profiling of mechanistically distinct enzyme classes using a common chemotype
    Gregory C Adam
    The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Nat Biotechnol 20:805-9. 2002
    ..These results indicate that activity-based probes compatible with whole-proteome analysis can be developed for numerous enzyme classes and applied to identify enzymes associated with discrete pathological states...
  97. pmc In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML29: antinociceptive activity without cannabimimetic side effects
    B M Ignatowska-Jankowska
    Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA
    Br J Pharmacol 171:1392-407. 2014
    ..Here, we tested the in vivo effects of one such compound, KML29 (1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(benzo[d][1,3]dioxol-5-yl)(hydroxy)methyl)piperidine-1-carboxylate)...
  98. ncbi request reprint Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry
    Allan Weber
    Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc, 2525 Dupont Drive, P O Box 19534, Irvine, CA 92623, USA
    J Lipid Res 45:757-63. 2004
    ..This report demonstrates that prostamides, including prostamide F(2alpha), were formed in vivo from anandamide, potentially by the cyclooxygenase-2 pathway when the competing FAAH pathway is lacking...
  99. ncbi request reprint Fatty acid amide hydrolase (-/-) mice exhibit an increased sensitivity to the disruptive effects of anandamide or oleamide in a working memory water maze task
    Stephen A Varvel
    Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, 23298 0613, USA
    J Pharmacol Exp Ther 317:251-7. 2006
    ..More generally, FAAH may represent a novel therapeutic target that circumvents the undesirable cognitive side effects commonly associated with direct-acting cannabinoid agonists...
  100. ncbi request reprint Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system
    Edward D Hogestatt
    Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, SE 221 85 Lund, Sweden
    J Biol Chem 280:31405-12. 2005
    ....
  101. pmc Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase
    Pal Pacher
    National Institutes of Health, NIAAA, Laboratory of Physiological Studies, 5625 Fishers Lane MSC 9413, Rm 2S24, Bethesda, MD 20892 9413, USA
    Am J Physiol Heart Circ Physiol 289:H533-41. 2005
    ....

Research Grants5

  1. STRUCTURE/FUNCTION STUDIES OF FATTY ACID AMIDE HYDROLASE
    Benjamin Cravatt; Fiscal Year: 2004
    ..abstract_text> ..
  2. Drug Abuse Related Polymorphism in Fatty Acid Amide Hydrolase
    Benjamin Cravatt; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  3. Microarray Platform for Profiling Cancer Proteases
    Benjamin Cravatt; Fiscal Year: 2008
    ..These proteases may in turn represent valuable new markers and targets for the diagnosis and treatment of cancer. ..
  4. CHEMICAL APPROACHES FOR ACTIVITY BASED PROTEOMICS
    Benjamin Cravatt; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  5. Enzymes That Regulate Fatty Acid Amide Function In Vivo
    Benjamin Cravatt; Fiscal Year: 2009
    ..These studies will elucidate the functions of key enzymes that regulate FAA signaling in vivo. These proteins may represent new targets for the treatment of pain, addiction, and other neurological disorders. ..