PALMER WILLIAM TAYLOR

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Cholinesterase confabs and cousins: Approaching forty years
    Palmer Taylor
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, Mail Code 0657, La Jolla, CA 92093, United States Electronic address
    Chem Biol Interact 203:10-3. 2013
  2. pmc Synthesis of selective agonists for the α7 nicotinic acetylcholine receptor with in situ click-chemistry on acetylcholine-binding protein templates
    John G Yamauchi
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA
    Mol Pharmacol 82:687-99. 2012
  3. pmc Contemporary paradigms for cholinergic ligand design guided by biological structure
    Palmer Taylor
    Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Bioorg Med Chem Lett 14:1875-7. 2004
  4. pmc Structure-guided drug design: conferring selectivity among neuronal nicotinic receptor and acetylcholine-binding protein subtypes
    Palmer Taylor
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0657, USA
    Biochem Pharmacol 74:1164-71. 2007
  5. pmc From Split to Sibenik: the tortuous pathway in the cholinesterase field
    Palmer Taylor
    Department of Pharmacology 0636, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 187:3-9. 2010
  6. ncbi request reprint Application of recombinant DNA methods for production of cholinesterases as organophosphate antidotes and detectors
    Palmer Taylor
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0657, USA
    Arh Hig Rada Toksikol 58:339-45. 2007
  7. pmc Acetylcholinesterase: converting a vulnerable target to a template for antidotes and detection of inhibitor exposure
    Palmer Taylor
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0650, USA
    Toxicology 233:70-8. 2007
  8. ncbi request reprint Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta
    Davide Comoletti
    Department of Pharmacology, University of California, La Jolla, California 92093 0636, USA
    J Biol Chem 278:50497-505. 2003
  9. pmc Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Biochem J 373:33-40. 2003
  10. ncbi request reprint Acrylodan-conjugated cysteine side chains reveal conformational state and ligand site locations of the acetylcholine-binding protein
    Ryan E Hibbs
    Department of Pharmacology, University of California San Diego, La Jolla, CA 92093 0636, USA
    J Biol Chem 279:28483-91. 2004

Research Grants

Collaborators

Detail Information

Publications65

  1. pmc Cholinesterase confabs and cousins: Approaching forty years
    Palmer Taylor
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, Mail Code 0657, La Jolla, CA 92093, United States Electronic address
    Chem Biol Interact 203:10-3. 2013
    ....
  2. pmc Synthesis of selective agonists for the α7 nicotinic acetylcholine receptor with in situ click-chemistry on acetylcholine-binding protein templates
    John G Yamauchi
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA
    Mol Pharmacol 82:687-99. 2012
    ....
  3. pmc Contemporary paradigms for cholinergic ligand design guided by biological structure
    Palmer Taylor
    Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Bioorg Med Chem Lett 14:1875-7. 2004
    ..Conformation and fluctuations in receptor structure are critical to ligand selectivity, and we present here how a flexible receptor template can be used in the development of selective ligands affecting cholinergic neurotransmission...
  4. pmc Structure-guided drug design: conferring selectivity among neuronal nicotinic receptor and acetylcholine-binding protein subtypes
    Palmer Taylor
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0657, USA
    Biochem Pharmacol 74:1164-71. 2007
    ....
  5. pmc From Split to Sibenik: the tortuous pathway in the cholinesterase field
    Palmer Taylor
    Department of Pharmacology 0636, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 187:3-9. 2010
    ..Those engaged in cholinesterase research should take great pride in our accomplishments punctuated by the series of ten meetings. The momentum established and initial studies with related proteins all hold great promise for the future...
  6. ncbi request reprint Application of recombinant DNA methods for production of cholinesterases as organophosphate antidotes and detectors
    Palmer Taylor
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0657, USA
    Arh Hig Rada Toksikol 58:339-45. 2007
    ....
  7. pmc Acetylcholinesterase: converting a vulnerable target to a template for antidotes and detection of inhibitor exposure
    Palmer Taylor
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0650, USA
    Toxicology 233:70-8. 2007
    ..Since external reagents do not have to be added to detect the fluorescence change, the modified enzyme would serve as a remote sensor...
  8. ncbi request reprint Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta
    Davide Comoletti
    Department of Pharmacology, University of California, La Jolla, California 92093 0636, USA
    J Biol Chem 278:50497-505. 2003
    ..We show here that glycosylation processing of neuroligin, in addition to mRNA splicing and gene selection, contributes to the specificity of the neurexin-beta/neuroligin-1 association...
  9. pmc Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Biochem J 373:33-40. 2003
    ..Rather, the individual aromatic residues may mutually interact to confer a distinctive stereospecificity pattern towards organophosphates...
  10. ncbi request reprint Acrylodan-conjugated cysteine side chains reveal conformational state and ligand site locations of the acetylcholine-binding protein
    Ryan E Hibbs
    Department of Pharmacology, University of California San Diego, La Jolla, CA 92093 0636, USA
    J Biol Chem 279:28483-91. 2004
    ..Labeling at other residue positions around the predicted binding pocket also reveals distinctive spectral changes for alpha-bungarotoxin, agonists, and alkaloid antagonists...
  11. ncbi request reprint Inhibitors of different structure induce distinguishing conformations in the omega loop, Cys69-Cys96, of mouse acetylcholinesterase
    Jianxin Shi
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 277:43301-8. 2002
    ..The fluorescence changes induced by the modified enzyme may prove useful in the detection of organophosphates or exposure to cholinesterase inhibitors...
  12. ncbi request reprint Structural and ligand recognition characteristics of an acetylcholine-binding protein from Aplysia californica
    Scott B Hansen
    Department of Pharmacology, University of California, San Diego, La Jolla 92093 0636, USA
    J Biol Chem 279:24197-202. 2004
    ..Hence, the two soluble proteins from mollusks, which can be studied by a variety of physical methods, become discrete surrogate proteins for the extracellular domains of distinct subtypes of nicotinic acetylcholine receptors...
  13. ncbi request reprint Influence of agonists and antagonists on the segmental motion of residues near the agonist binding pocket of the acetylcholine-binding protein
    Ryan E Hibbs
    Department of Pharmacology, University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 281:39708-18. 2006
    ..The results reveal that agonists and antagonists produced distinctive changes in the flexibility of a portion of loop F...
  14. ncbi request reprint Nanosecond dynamics of acetylcholinesterase near the active center gorge
    Aileen E Boyd
    Department of Pharmacology, University of California, La Jolla, California 92093 0636, USA
    J Biol Chem 279:26612-8. 2004
    ....
  15. ncbi request reprint The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing
    Davide Comoletti
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    J Neurosci 24:4889-93. 2004
    ..Other substitutions for Arg451 allow for normal cellular expression but diminished affinity for NX1beta. Our findings reveal a cellular phenotype and loss of function for a congenital mutation associated with autistic spectrum disorders...
  16. pmc Atomic interactions of neonicotinoid agonists with AChBP: molecular recognition of the distinctive electronegative pharmacophore
    Todd T Talley
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 99093 0657, USA
    Proc Natl Acad Sci U S A 105:7606-11. 2008
    ..This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids...
  17. ncbi request reprint A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family
    Antonella De Jaco
    Department of Pharmacology, University of California San Diego, La Jolla, California 92093 0636, USA
    J Biol Chem 281:9667-76. 2006
    ..The mutation may alter the capacity of these proteins to dissociate from their chaperone prior to oligomerization and processing for export...
  18. ncbi request reprint Defining nicotinic agonist binding surfaces through photoaffinity labeling
    Motohiro Tomizawa
    Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720 3112, USA
    Biochemistry 46:8798-806. 2007
    ..These findings enabled us to use AChBP as a structural surrogate to define the nAChR agonist site...
  19. ncbi request reprint Mutation of acetylcholinesterase to enhance oxime-assisted catalytic turnover of methylphosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Toxicology 233:79-84. 2007
    ..Our results confirm that a mixture of a mutant enzyme and an oxime might serve as an in vivo catalytic scavenger of organophosphates...
  20. ncbi request reprint Ligand-induced conformational changes in the acetylcholine-binding protein analyzed by hydrogen-deuterium exchange mass spectrometry
    Jianxin Shi
    Department of Pharmacology and Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 281:12170-7. 2006
    ..These results reveal dynamic states and fluctuating movements in the vicinity of the binding site for unligated AChBP that can be influenced selectively by ligands...
  21. ncbi request reprint Residues in the epsilon subunit of the nicotinic acetylcholine receptor interact to confer selectivity of waglerin-1 for the alpha-epsilon subunit interface site
    Brian E Molles
    Department of Pharmacology, Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA92093 0636, USA
    Biochemistry 41:7895-906. 2002
    ..We use the binding and interaction energies for Wtx-1 to generate structural models of the alpha-epsilon, alpha-gamma, and alpha-delta binding sites containing the nonhomologous insertion...
  22. pmc Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family
    Antonella De Jaco
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 285:28674-82. 2010
    ..Our results suggest that disease-related mutations in the alpha/beta-hydrolase fold domain share common trafficking deficiencies yet lead to discrete congenital disorders of differing severity in the endocrine and nervous systems...
  23. pmc Atypical nicotinic agonist bound conformations conferring subtype selectivity
    Motohiro Tomizawa
    Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720 3112, USA
    Proc Natl Acad Sci U S A 105:1728-32. 2008
    ..Accordingly, the subtype selectivity is based on two disparate bound conformations of nicotinic agonists, thereby establishing an atypical concept for neonicotinoid versus nicotinoid selectivity between insect and vertebrate nAChRs...
  24. ncbi request reprint Structural dynamics of the alpha-neurotoxin-acetylcholine-binding protein complex: hydrodynamic and fluorescence anisotropy decay analyses
    Ryan E Hibbs
    Department of Pharmacology and Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 44:16602-11. 2005
    ..The results indicate that bound alpha-neurotoxin is not rigidly oriented on the surface of AChBP but rather exhibits segmental motion by virtue of flexibility in its fingerlike structure...
  25. ncbi request reprint Mutant cholinesterases possessing enhanced capacity for reactivation of their phosphonylated conjugates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 43:3222-9. 2004
    ..Rates of reactivation reach values sufficient for consideration of mixtures of a mutant enzyme and an oxime as a scavenging strategy in protection and treatment of organophosphate exposure...
  26. pmc Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations
    Scott B Hansen
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    EMBO J 24:3635-46. 2005
    ..This comprehensive set of structures reflects a dynamic template for delineating further conformational changes of the LBD of the nicotinic receptor...
  27. pmc An ion selectivity filter in the extracellular domain of Cys-loop receptors reveals determinants for ion conductance
    Scott B Hansen
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093 0650, USA
    J Biol Chem 283:36066-70. 2008
    ....
  28. pmc Nicotinic agonist binding site mapped by methionine- and tyrosine-scanning coupled with azidochloropyridinyl photoaffinity labeling
    Motohiro Tomizawa
    Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720 3112, USA
    J Med Chem 52:3735-41. 2009
    ..Methionine and tyrosine are the only residues found derivatized, and their reactivity exquisitely depends on the direction of the azido moiety and its apposition to the reactive amino acid side chains...
  29. pmc Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor
    Ryan E Hibbs
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
    EMBO J 28:3040-51. 2009
    ....
  30. ncbi request reprint Nanosecond dynamics of the mouse acetylcholinesterase cys69-cys96 omega loop
    Jianxin Shi
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    J Biol Chem 278:30905-11. 2003
    ....
  31. ncbi request reprint Structural characterization of recombinant soluble rat neuroligin 1: mapping of secondary structure and glycosylation by mass spectrometry
    Ross C Hoffman
    Department of Pharmacology and Howard Hughes Medical Institute Mass Spectrometry Facility, University of California, San Diego, La Jolla 92093, USA
    Biochemistry 43:1496-506. 2004
    ..From predictions based on sequence homology of NL1 to acetylcholinesterase and the molecular features of NL1 established from mass spectrometric analysis, a novel topology model for NL three-dimensional structure has been constructed...
  32. pmc Galanthamine and non-competitive inhibitor binding to ACh-binding protein: evidence for a binding site on non-alpha-subunit interfaces of heteromeric neuronal nicotinic receptors
    Scott B Hansen
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0650, USA
    J Mol Biol 369:895-901. 2007
    ....
  33. pmc LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation
    Joris De Wit
    Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA
    Neuron 64:799-806. 2009
    ..These observations indicate that an LRRTM2-Neurexin1 interaction plays a critical role in regulating excitatory synapse development...
  34. pmc Investigating the structural influence of surface mutations on acetylcholinesterase inhibition by organophosphorus compounds and oxime reactivation
    Tuba Küçükkilinç
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 187:238-40. 2010
    ..These results indicate that selected residues outside the active center influence inhibition, reactivation and catalysis rates through longer range interactions...
  35. pmc Acetylcholinesterase expression in muscle is specifically controlled by a promoter-selective enhancesome in the first intron
    Shelley Camp
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093 0650, USA
    J Neurosci 28:2459-70. 2008
    ....
  36. ncbi request reprint In situ click chemistry: enzyme inhibitors made to their own specifications
    Roman Manetsch
    Contribution from the Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Am Chem Soc 126:12809-18. 2004
    ..All in situ-generated compounds were extremely potent AChE inhibitors, because of the presence of multiple sites of interaction, which include the newly formed triazole nexus as a significant pharmacophore...
  37. pmc Spectroscopic analysis of benzylidene anabaseine complexes with acetylcholine binding proteins as models for ligand-nicotinic receptor interactions
    Todd T Talley
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 45:8894-902. 2006
    ....
  38. ncbi request reprint Alpha-conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as well as alpha3beta2 and alpha7 nicotinic acetylcholine receptors
    Todd T Talley
    Department of Pharmacology, University of California, La Jolla, California 92093 0636, USA
    J Biol Chem 281:24678-86. 2006
    ....
  39. pmc Tryptophan fluorescence reveals conformational changes in the acetylcholine binding protein
    Scott B Hansen
    Department of Pharmacology, University of California, San Diego, La Jolla 92093 0636, USA
    J Biol Chem 277:41299-302. 2002
    ..Thus, the marked tryptophan quenching not only documents the importance of aromatic residues in ligand recognition, but establishes that the AChBP will be a useful functional as well as structural surrogate of the nicotinic receptor...
  40. pmc Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion
    Arthur T Suckow
    Department of Medicine, Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California 92093, USA
    Endocrinology 149:6006-17. 2008
    ..Analogous to their role in synaptic neurotransmission, neurexin-neuroligin interactions may play a role in the formation of the submembrane insulin secretory apparatus...
  41. pmc Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24: influence on heritable autonomic traits in twin pairs
    Brinda K Rana
    Departments of Psychiatry, University of California at San Diego, La Jolla, California 92093 0657, USA
    J Pharmacol Exp Ther 331:419-28. 2009
    ..These cellular events suggest a homeostatic mechanism underlying the pleiotropic actions of CHRNA3 genetic variation on autonomic function observed in twins...
  42. ncbi request reprint Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of Waglerin-1 for nicotinic acetylcholine receptors
    Brian E Molles
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    J Biol Chem 277:5433-40. 2002
    ..The overall results show that non-conserved residues at the nAChR binding site, although not crucial for activation by ACh, govern the potency of neuromuscular toxins...
  43. ncbi request reprint Nicotinic acetylcholine receptor distribution in relation to spinal neurotransmission pathways
    Imran Khan
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
    J Comp Neurol 467:44-59. 2003
    ..These studies reveal a dense and distinguishable distribution of nAChR subunits in the spinal cord and point toward future therapeutic targeting for specific spinal actions...
  44. pmc Contributions of selective knockout studies to understanding cholinesterase disposition and function
    Shelley Camp
    Department Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences 0657, University of California San Diego, La Jolla, CA 92093 0657, USA
    Chem Biol Interact 187:72-7. 2010
    ..The studies generated by these knockout mouse strains have yielded valuable insights into the function and localization of AChE in mammalian systems that cannot be approached in cell culture or in vitro...
  45. ncbi request reprint Direct analysis of the kinetic profiles of organophosphate-acetylcholinesterase adducts by MALDI-TOF mass spectrometry
    Lori L Jennings
    Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA
    Biochemistry 42:11083-91. 2003
    ..For dimethyl phosphorylated AChE, OP exposure has been monitored by the ratio of tryptic peptide peaks that correspond to unmodified (uninhibited and/or reactivated), inhibited, and aged enzyme...
  46. pmc Interaction kinetics of oximes with native, phosphylated and aged human acetylcholinesterase
    Zoran Radic
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093 0650, United States
    Chem Biol Interact 187:163-6. 2010
    ..Dealkylation of phosphonylated enzyme, however opens space in the gorge allowing oximes to bind tighter...
  47. ncbi request reprint Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks
    Warren G Lewis
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 41:1053-7. 2002
  48. ncbi request reprint Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness
    Imran M Khan
    Department of Pharmacology, University of California, San Diego, California 92093 0636, USA
    Physiol Genomics 11:65-72. 2002
    ....
  49. pmc The macromolecular architecture of extracellular domain of alphaNRXN1: domain organization, flexibility, and insights into trans-synaptic disposition
    Davide Comoletti
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA
    Structure 18:1044-53. 2010
    ..We thus provide the first structural insights into the architecture of the extracellular region of neurexin-1alpha, show how the protein may fit in the synaptic cleft, and how partnering proteins could bind simultaneously...
  50. ncbi request reprint Structural dynamics of the acetylcholine binding protein: hydrodynamic and fluorescence anisotropy decay analyses
    Ryan E Hibbs
    Department of Pharmacology, University of California San Diego, La Jolla, CA 92093 0636, USA
    J Mol Neurosci 30:73-4. 2006
    ..As a structural and functional surrogate of the nicotinic acetylcholine receptor, the AChBP reveals ligand-mediated changes in conformation, mimicking that of the receptor...
  51. pmc A virtual screening study of the acetylcholine binding protein using a relaxed-complex approach
    Arneh Babakhani
    Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Dr MC 0365, La Jolla, CA 92093 0365, USA
    Comput Biol Chem 33:160-70. 2009
    ..These novel ligands could serve as potential pharmaceuticals in the AChBP/nAChR systems...
  52. pmc Tetrameric mouse acetylcholinesterase: continuum diffusion rate calculations by solving the steady-state Smoluchowski equation using finite element methods
    Deqiang Zhang
    Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093, USA
    Biophys J 88:1659-65. 2005
    ..This study also shows that the finite element solver is well suited for solving the diffusion problem within complicated geometries...
  53. pmc Synaptic arrangement of the neuroligin/beta-neurexin complex revealed by X-ray and neutron scattering
    Davide Comoletti
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA
    Structure 15:693-705. 2007
    ..As mutations of neurexin and neuroligin genes appear to be linked to autism, these models provide a structural framework for understanding altered recognition by these proteins in neurodevelopmental disorders...
  54. pmc Conformational transitions in protein-protein association: binding of fasciculin-2 to acetylcholinesterase
    Jennifer M Bui
    Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093 0365, USA
    Biophys J 90:3280-7. 2006
    ..It seems likely that the more stable apo form binds rapidly to AChE and conformational readjustments then occur in the resulting encounter complex...
  55. ncbi request reprint Molecular basis of interactions of cholinesterases with tight binding inhibitors
    Zoran Radic
    Department of Pharmacology 0636, University of California at San Diego, La Jolla, CA 92093, USA
    Chem Biol Interact 157:133-41. 2005
    ..These tight binding inhibitor interactions reveal useful information not only on the conformational flexibility of ChEs, but also on the diversity of modes of interaction that achieve inhibition...
  56. ncbi request reprint Influence of the 5' intron in the control of acetylcholinesterase gene expression during myogenesis
    Antonella De Jaco
    Department of Pharmacology, University of California San Diego, La Jolla, CA 92093 0636, USA
    Chem Biol Interact 157:372-3. 2005
    ..Marquez, B. de La Torre, J.M. Long, G. Bucht, P. Taylor, Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion, VIII IMC Proceedings]...
  57. ncbi request reprint A single mutation near the C-terminus in alpha/beta hydrolase fold protein family causes a defect in protein processing
    Antonella De Jaco
    Department of Pharmacology and National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, CA 92093 0636, USA
    Chem Biol Interact 157:371-2. 2005
    ....
  58. ncbi request reprint Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion
    Shelley Camp
    University of California, San Diego, 9500 Gilman Dr, Department of Pharmacology, La Jolla, CA 92093 0636, USA
    Chem Biol Interact 157:79-86. 2005
    ..Rizzino, R.D. McComb, P. Taylor, S.H. Hinrichs, O. Lockridge, Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J. Pharmacol. Exp. Ther. 293 (3) (2000) 896-902]...
  59. ncbi request reprint Ablation of primary afferent terminals reduces nicotinic receptor expression and the nociceptive responses to nicotinic agonists in the spinal cord
    Imran M Khan
    Department of Pharmacology, University of California, San Diego, CA 92093 0636, USA
    J Neurocytol 33:543-56. 2004
    ..Conversely, spinal nicotinic receptors not located on C-fibers play a primary role in the spinal pathways evoking spinally coordinated autonomic cardiovascular responses...
  60. pmc Characterization of the solution structure of a neuroligin/beta-neurexin complex
    Davide Comoletti
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 175:150-5. 2008
    ....
  61. pmc Trafficking of cholinesterases and neuroligins mutant proteins. An association with autism
    Antonella De Jaco
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093 0657, USA
    Chem Biol Interact 175:349-51. 2008
    ..We identified several proteins belonging to distinct ER resident chaperones families, including calnexin, responsible for playing a role in the folding steps of the AChE and NLs...
  62. pmc Probing gorge dimensions of cholinesterases by freeze-frame click chemistry
    Zoran Radic
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0650, USA
    Chem Biol Interact 175:161-5. 2008
    ..Thus, in addition to synthesizing high affinity, lead inhibitors in situ, freeze-frame, click chemistry has capacity to generate species-specific AChE ligands that conform to the determinants in the gorge...
  63. pmc Ligand-induced conformational change in the alpha7 nicotinic receptor ligand binding domain
    Richard H Henchman
    Howard Hughes Medical Institute, NSF Center for Theoretical Biophysics, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA
    Biophys J 88:2564-76. 2005
    ....
  64. doi request reprint Folding anomalies of neuroligin3 caused by a mutation in the alpha/beta-hydrolase fold domain
    Antonella De Jaco
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, United States
    Chem Biol Interact 187:56-8. 2010
    ..These findings highlight the role of proper protein folding in protein processing and localization...
  65. pmc Naturally occurring variations in the human cholinesterase genes: heritability and association with cardiovascular and metabolic traits
    Anne M Valle
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California 92093 0657, USA
    J Pharmacol Exp Ther 338:125-33. 2011
    ..A substantial fraction of the D134H instability could be reversed in the D134H/R136Q mutant. Hence, common genetic variations at ACHE and BCHE loci were associated with changes in corresponding enzymatic activities in blood...

Research Grants13

  1. FACILITIES CONSTRUCTION CENTERALIZED PHARMCOGENOMICS
    Palmer Taylor; Fiscal Year: 2003
    ..The Centralized Animal Facility is critically needed to support this effort and allow economies of scale for animal research. ..
  2. KINETICS OF DRUG MACROMOLECULE COMPLEX FORMATION
    PALMER WILLIAM TAYLOR; Fiscal Year: 2010
    ....
  3. Oxime-Assisted Catalysis of Organophosphates and Reactivation of AChE
    Palmer Taylor; Fiscal Year: 2007
    ..Hence, our approach will both augment catalytic scavenging of organophosphates in the circulation and enhance reactivation at the target tissues. ..
  4. GRADUATE TRAINING IN CELLULAR AND MOLECULAR PHARMACOLOGY
    Palmer Taylor; Fiscal Year: 2007
    ..abstract_text> ..
  5. Nicotinic Receptor Template-guided Drug Design
    Palmer Taylor; Fiscal Year: 2007
    ..The final stages of investigation will include studies in rodents to determine efficacy and toxicity. ..
  6. KINETICS OF DRUG MACROMOLECULE COMPLEX FORMATION
    Palmer Taylor; Fiscal Year: 2007
    ..abstract_text> ..
  7. KINETICS OF DRUG MACROMOLECULE COMPLEX FORMATION
    PALMER WILLIAM TAYLOR; Fiscal Year: 2011
    ....