David Christianson

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Structural biology and chemistry of the terpenoid cyclases
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    Chem Rev 106:3412-42. 2006
  2. pmc Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis
    Mustafa Köksal
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    Nature 469:116-20. 2011
  3. pmc Structure and mechanism of the diterpene cyclase ent-copalyl diphosphate synthase
    Mustafa Köksal
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Chem Biol 7:431-3. 2011
  4. ncbi request reprint Chemistry. Roots of biosynthetic diversity
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 316:60-1. 2007
  5. ncbi request reprint Biochemistry. Five golden rings
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Science 311:1382-3. 2006
  6. pmc Unearthing the roots of the terpenome
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104 6323, United States
    Curr Opin Chem Biol 12:141-50. 2008
  7. pmc Crystal structure of lactaldehyde dehydrogenase from Escherichia coli and inferences regarding substrate and cofactor specificity
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Mol Biol 366:481-93. 2007
  8. ncbi request reprint Stereochemistry of guanidine-metal interactions: implications for L-arginine-metal interactions in protein structure and function
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Proteins 65:637-42. 2006
  9. pmc Mechanistic inferences from the binding of ligands to LpxC, a metal-dependent deacetylase
    Heather A Gennadios
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 45:7940-8. 2006
  10. ncbi request reprint Molecular recognition of the substrate diphosphate group governs product diversity in trichodiene synthase mutants
    L Sangeetha Vedula
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 44:6153-63. 2005

Research Grants

  1. STRUCTURE/FUNCTION OF CARBONIC ANHYDRASE
    David Christianson; Fiscal Year: 2001
  2. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2005
  3. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2009
  4. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2009
  5. STRUCTURE/FUNCTION OF EPOXIDE HYDROLASE
    David Christianson; Fiscal Year: 2005
  6. Structure and Function of Biosynthetic Enzymes
    David W Christianson; Fiscal Year: 2010
  7. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2002
  8. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 1999
  9. STRUCTURE/FUNCTION OF CARBONIC ANHYDRASE
    David Christianson; Fiscal Year: 1999
  10. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2004

Collaborators

  • David E Ash
  • Huayou Hu
  • Robert Coates
  • RONALD VIOLA
  • Rudolf K Allemann
  • Bernd Ensing
  • Michael L Klein
  • Flora Meilleur
  • Jesse A May
  • Youhai Chen
  • Alfonso Mora
  • Abdulamaged M Traish
  • Daniel Mansuy
  • J M Hare
  • Matteo Dal Peraro
  • D J Miller
  • G M Whitesides
  • TREVOR PENNING
  • Luigi Di Costanzo
  • Douglas A Whittington
  • Evis Cama
  • L Sangeetha Vedula
  • David E Cane
  • Hyunshun Shin
  • Heather A Gennadios
  • German A Gomez
  • Kevin M Jude
  • Mustafa Köksal
  • Ekaterina Y Shishova
  • Frances A Emig
  • Sungwoo Ryoo
  • Chu Young Kim
  • Lakshmi Santhanam
  • D K Srivastava
  • Carol A Fierke
  • Diana M Colleluori
  • Noel N Kim
  • Michael J Rynkiewicz
  • Julie A Aaron
  • Tatiana Y Zakharian
  • Artin Shoukas
  • Hyun Kyo Lim
  • Yuxin Zhao
  • Daniel Nyhan
  • Dan E Berkowitz
  • Vijay M Krishnamurthy
  • Marco De Vivo
  • Abir L Banerjee
  • Sumathra Manokaran
  • Sanku Mallik
  • Christophe Morisseau
  • Bruce D Hammock
  • Marcy Hernick
  • Shoufa Han
  • Kristin M Rusche
  • Lingyun Xu
  • Bartosz A Grzybowski
  • Myriam Seemann
  • Yinghua Jin
  • Reuben J Peters
  • Rodney Croteau
  • Hunter C Champion
  • Juan A Faraldos
  • Andre Camara
  • Tatiana Zakharian
  • Ivan J Dmochowski
  • Gaurav Gupta
  • Alexandre Benjo
  • Hyun Kyung Lim
  • David Huso
  • Jennifer M Chambers
  • Ezra Baraban
  • Jiaoyang Jiang
  • Gary Gerstenblith
  • Gautam Sikka
  • Eric Tuday
  • Jason E Drury
  • Monica Ilies
  • Kevin Soucy
  • Jayson Sohi
  • Fanglei Yu
  • Nicholas J Alp
  • Joel Kooren
  • Michael Haertlein
  • Hyun Kyoung Lim
  • Manas Haldar
  • Kaikobad Irani
  • Victor Miriel
  • Richard Rivers
  • Brooks R Bohall

Detail Information

Publications49

  1. ncbi request reprint Structural biology and chemistry of the terpenoid cyclases
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    Chem Rev 106:3412-42. 2006
  2. pmc Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis
    Mustafa Köksal
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    Nature 469:116-20. 2011
    ..A class II cyclase activates the isoprenoid substrate by protonation instead of ionization, and the TXS structure reveals a definitive connection between the two distinct cyclase classes in the evolution of terpenoid biosynthesis...
  3. pmc Structure and mechanism of the diterpene cyclase ent-copalyl diphosphate synthase
    Mustafa Köksal
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Chem Biol 7:431-3. 2011
    ..Modular domain architecture in plant diterpene cyclases enables the evolution of alternative active sites and chemical strategies for catalyzing isoprenoid cyclization reactions...
  4. ncbi request reprint Chemistry. Roots of biosynthetic diversity
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 316:60-1. 2007
  5. ncbi request reprint Biochemistry. Five golden rings
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Science 311:1382-3. 2006
  6. pmc Unearthing the roots of the terpenome
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104 6323, United States
    Curr Opin Chem Biol 12:141-50. 2008
    ....
  7. pmc Crystal structure of lactaldehyde dehydrogenase from Escherichia coli and inferences regarding substrate and cofactor specificity
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Mol Biol 366:481-93. 2007
    ....
  8. ncbi request reprint Stereochemistry of guanidine-metal interactions: implications for L-arginine-metal interactions in protein structure and function
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Proteins 65:637-42. 2006
    ..Although such interactions are rare, this analysis serves as a useful reference point for the growing interest in enzymes containing L-arginine residues that function as general bases or metal ligands...
  9. pmc Mechanistic inferences from the binding of ligands to LpxC, a metal-dependent deacetylase
    Heather A Gennadios
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 45:7940-8. 2006
    ..These results suggest that the native state of this metallohydrolase may contain a pentacoordinate zinc ion, which contrasts with the native states of archetypical zinc hydrolases such as thermolysin and carboxypeptidase A...
  10. ncbi request reprint Molecular recognition of the substrate diphosphate group governs product diversity in trichodiene synthase mutants
    L Sangeetha Vedula
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 44:6153-63. 2005
    ....
  11. pmc Human soluble epoxide hydrolase: structural basis of inhibition by 4-(3-cyclohexylureido)-carboxylic acids
    German A Gomez
    Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Protein Sci 15:58-64. 2006
    ....
  12. pmc Proton shuttles and phosphatase activity in soluble epoxide hydrolase
    Marco De Vivo
    Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    J Am Chem Soc 129:387-94. 2007
    ..Moreover, due to the conservation of structural features in the N-terminal catalytic site of sEH and other members of the HAD superfamily, we suggest a generalization of our findings to these other metal-dependent phosphatases...
  13. pmc X-ray crystal structure of aristolochene synthase from Aspergillus terreus and evolution of templates for the cyclization of farnesyl diphosphate
    Ekaterina Y Shishova
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 46:1941-51. 2007
    ..Across the greater family of terpenoid cyclases, this template is highly evolvable within a conserved alpha-helical fold for the synthesis of terpene natural products of diverse structure and stereochemistry...
  14. pmc Crystal structure of human arginase I complexed with thiosemicarbazide reveals an unusual thiocarbonyl mu-sulfide ligand in the binuclear manganese cluster
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Am Chem Soc 129:6388-9. 2007
  15. pmc Expression, purification, assay, and crystal structure of perdeuterated human arginase I
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Arch Biochem Biophys 465:82-9. 2007
    ..Therefore, we conclude that crystals of the perdeuterated human arginase I-ABH complex are suitable for neutron crystallographic study...
  16. pmc Exploring biosynthetic diversity with trichodiene synthase
    L Sangeetha Vedula
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Arch Biochem Biophys 466:260-6. 2007
    ....
  17. ncbi request reprint Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction
    Lakshmi Santhanam
    Johns Hopkins University School of Medicine, 720 Rutland Ave, Traylor 621, Baltimore MD 21209, USA
    Circ Res 101:692-702. 2007
    ..These findings suggest that S-nitrosylated arginase1 can compete with NOS for L-arginine and contribute to endothelial dysfunction in the aging cardiovascular system...
  18. doi request reprint Endothelial arginase II: a novel target for the treatment of atherosclerosis
    Sungwoo Ryoo
    Department of Anesthesiology Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
    Circ Res 102:923-32. 2008
    ..These data indicate that arginase II plays a critical role in the pathophysiology of cholesterol-mediated endothelial dysfunction and represents a novel target for therapy in atherosclerosis...
  19. pmc X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis
    Ekaterina Y Shishova
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Biol Chem 283:15431-9. 2008
    ..Taken together, these structures provide 12 independent "snapshots" of substrate or product complexes that suggest a possible sequence for metal ion binding and conformational changes required for catalysis...
  20. pmc Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    J Biol Chem 283:16830-9. 2008
    ..The locations of disease-linked mutations thought to be responsible for bile acid deficiency are also revealed...
  21. ncbi request reprint Probing the role of the hyper-reactive histidine residue of arginase
    Diana M Colleluori
    Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Arch Biochem Biophys 444:15-26. 2005
    ..H141 is proposed to serve as an acid/base catalyst, deprotonating the metal-bridging water molecule to generate the metal-bridging hydroxide nucleophile, and by protonating the amino group of the product to facilitate its departure...
  22. pmc Role of arginine-304 in the diphosphate-triggered active site closure mechanism of trichodiene synthase
    L Sangeetha Vedula
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 44:12719-27. 2005
    ..Structural analysis of the R304K mutant and comparison with the monoterpene cyclase (+)-bornyl diphosphate synthase suggest that the significant loss in activity results from compromised activation of the PP(i) leaving group...
  23. ncbi request reprint Design of amino acid sulfonamides as transition-state analogue inhibitors of arginase
    Evis Cama
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Am Chem Soc 125:13052-7. 2003
    ....
  24. ncbi request reprint Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis
    German A Gomez
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 43:4716-23. 2004
    ..Natl. Acad. Sci. U.S.A. 100, 1558-1563]. The binding of Mg(2+)-HPO4(2-) to the N-terminal domain of human sEH in its CIU complex reveals structural features relevant to those of the enzyme-substrate complex in the phosphatase reaction...
  25. pmc Arginase and autoimmune inflammation in the central nervous system
    Lingyun Xu
    Departments of Pathology and Laboratory Medicine and Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
    Immunology 110:141-8. 2003
    ..These results indicate that arginase plays important roles in autoimmune inflammation in the central nervous system...
  26. ncbi request reprint Human arginase II: crystal structure and physiological role in male and female sexual arousal
    Evis Cama
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 42:8445-51. 2003
    ..Therefore, arginase II is a potential target for the treatment of male and female sexual arousal disorders...
  27. ncbi request reprint Structural and functional importance of first-shell metal ligands in the binuclear manganese cluster of arginase I
    Evis Cama
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 42:7748-58. 2003
    ..F., Scolnick, L. R., Ash, D. E., and Christianson, D. W. (1996) Nature 383, 554-557)...
  28. pmc Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis
    Douglas A Whittington
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Proc Natl Acad Sci U S A 100:8146-50. 2003
    ..Notably, simple inhibitors designed to target interactions in the hydrophobic tunnel bind with micromolar affinity, thereby representing a step toward the structure-based design of a potent, broad-spectrum antibacterial drug...
  29. pmc Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase
    Douglas A Whittington
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia 19104 6323, USA
    Proc Natl Acad Sci U S A 99:15375-80. 2002
    ..Structures of complexes with aza analogues of substrate and carbocation intermediates, as well as complexes with pyrophosphate and bornyl diphosphate, provide "snapshots" of the terpene cyclization cascade...
  30. ncbi request reprint X-ray crystal structures of D100E trichodiene synthase and its pyrophosphate complex reveal the basis for terpene product diversity
    Michael J Rynkiewicz
    Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 41:1732-41. 2002
    ....
  31. ncbi request reprint Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes
    Douglas A Whittington
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 279:7223-8. 2004
    ....
  32. ncbi request reprint Design of amino acid aldehydes as transition-state analogue inhibitors of arginase
    Hyunshun Shin
    Contribution from the Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Am Chem Soc 126:10278-84. 2004
    ..The binding mode of the neutral gem-diol may mimic the binding of the neutral tetrahedral intermediate and its flanking transition states in arginase catalysis...
  33. pmc Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response
    Luigi Di Costanzo
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Proc Natl Acad Sci U S A 102:13058-63. 2005
    ..This work serves as a foundation for studying the structural and chemical biology of arginase I in the immune response, and we demonstrate the inhibition of arginase activity by ABH in human and murine myeloid cells...
  34. ncbi request reprint UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase functions through a general acid-base catalyst pair mechanism
    Marcy Hernick
    Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 280:16969-78. 2005
    ..These structural features suggest that LpxC catalyzes deacetylation by using Glu78 and His265 as a general acid-base pair and the zinc-bound water as a nucleophile...
  35. ncbi request reprint Inhibitor coordination interactions in the binuclear manganese cluster of arginase
    Evis Cama
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 43:8987-99. 2004
    ....
  36. ncbi request reprint Crystal structure of F65A/Y131C-methylimidazole carbonic anhydrase V reveals architectural features of an engineered proton shuttle
    Kevin M Jude
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    Biochemistry 41:2485-91. 2002
    ....
  37. ncbi request reprint Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV
    Chu Young Kim
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    J Med Chem 45:888-93. 2002
    ..This study demonstrates how experimental structure determination methods and computational structure prediction methods can be used together to answer questions that cannot be answered by either method alone...
  38. pmc Combinatorial computational method gives new picomolar ligands for a known enzyme
    Bartosz A Grzybowski
    Harvard University, Department of Chemistry and Chemical Biology, 12 Oxford Street, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 99:1270-3. 2002
    ..The designed R isomer is the best-known inhibitor (K(d) approximately 30 pM) of human carbonic anhydrase II...
  39. pmc Structure of a 129Xe-cryptophane biosensor complexed with human carbonic anhydrase II
    Julie A Aaron
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323, USA
    J Am Chem Soc 130:6942-3. 2008
    ..The crystal structure confirms binding measurements indicating that the cryptophane cage does not strongly interact with the surface of the protein, which may enhance the sensitivity of 129Xe NMR spectroscopic measurements in solution...
  40. pmc Synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid and structure of its metal-bridging complex with human arginase I
    Tatiana Y Zakharian
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Org Biomol Chem 6:3240-3. 2008
    ..The synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid is reported along with the X-ray crystal structure of its complex with human arginase I, revealing unique coordination interactions with two manganese ions in the enzyme active site...
  41. ncbi request reprint Pentalenene synthase. Analysis of active site residues by site-directed mutagenesis
    Myriam Seemann
    Department of Chemistry, Box H, Brown University, Providence, Rhode Island 02912 9108, USA
    J Am Chem Soc 124:7681-9. 2002
    ..Finally, the F77Y mutant had a k(cat)/K(m) which was reduced by 20-fold compared to that of the wild-type synthase...
  42. pmc Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with "two-prong" inhibitors reveal the molecular basis of high affinity
    Kevin M Jude
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Am Chem Soc 128:3011-8. 2006
    ..This work provides the first evidence verifying the structural basis of nanomolar affinity measured for two-prong inhibitors targeting the carbonic anhydrases...
  43. pmc Structural and mechanistic analysis of trichodiene synthase using site-directed mutagenesis: probing the catalytic function of tyrosine-295 and the asparagine-225/serine-229/glutamate-233-Mg2+B motif
    L Sangeetha Vedula
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 6323, USA
    Arch Biochem Biophys 469:184-94. 2008
    ..In addition, the kinetic and structural properties of the Y295F mutant of trichodiene synthase were found to be similar to those of the wild-type enzyme, thereby ruling out a proposed role for Y295 in catalysis...
  44. ncbi request reprint Arginase: structure, mechanism, and physiological role in male and female sexual arousal
    David W Christianson
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104 6323, USA
    Acc Chem Res 38:191-201. 2005
    ..Therefore, arginase is a potential therapeutic target for the treatment of sexual arousal disorders in men and women...
  45. ncbi request reprint Role of arginase in the male and female sexual arousal response
    Noel N Kim
    Department of Urology and Institute for Sexual Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    J Nutr 134:2873S-2879S; discussion 2895S. 2004
    ....
  46. pmc Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding
    Heather A Gennadios
    Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6323
    Biochemistry 45:15216-23. 2006
    ..The structures of the LpxC-UDP and LpxC-pyrophosphate complexes provide new insights with regard to substrate recognition in the basic patch and metal ion coordination in the active site of LpxC...
  47. pmc Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II
    D K Srivastava
    Department of Chemistry and Molecular Biology, North Dakota State University, Fargo, North Dakota 58105, USA
    J Am Chem Soc 129:5528-37. 2007
    ..This contrasting behavior may arise in part from differences in active site desolvation and the conformational entropy of inhibitor binding to each isozyme active site...
  48. ncbi request reprint Amphipathic benzoic acid derivatives: synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC
    Hyunshun Shin
    Department of Chemistry, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117 1080, USA
    Bioorg Med Chem 15:2617-23. 2007
    ..We conclude that the intermolecular interactions in the hydrophobic tunnel dominate enzyme affinity in this series of benzoic acid derivatives...
  49. pmc Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II
    Vijay M Krishnamurthy
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA
    Chem Asian J 2:94-105. 2007
    ..Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by 19F NMR spectroscopy and X-ray crystallography (for complexes with human carbonic anhydrase II)...

Research Grants35

  1. STRUCTURE/FUNCTION OF CARBONIC ANHYDRASE
    David Christianson; Fiscal Year: 2001
    ..The proposed work will answer the question: what structural features constitute an effective catalytic proton shuttle site in an enzyme? ..
  2. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2005
    ..New inhibitor designs may exhibit enhanced properties such as affinity and membrane permeability, which may facilitate physiological studies of arginase inhibition in the laboratories of our collaborators. ..
  3. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2009
    ..abstract_text> ..
  4. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2009
    ....
  5. STRUCTURE/FUNCTION OF EPOXIDE HYDROLASE
    David Christianson; Fiscal Year: 2005
    ..abstract_text> ..
  6. Structure and Function of Biosynthetic Enzymes
    David W Christianson; Fiscal Year: 2010
    ....
  7. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2002
    ..abstract_text> ..
  8. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 1999
    ..Additionally, using arginase as the prototype, we will continue the development of a structure-based rationale for the design and synthesis and potent metalloenzyme inhibitors that target bimetallic clusters. ..
  9. STRUCTURE/FUNCTION OF CARBONIC ANHYDRASE
    David Christianson; Fiscal Year: 1999
    ..The proposed work will answer the question: what structural features constitute an effective catalytic proton shuttle site in an enzyme? ..
  10. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2004
    ..abstract_text> ..
  11. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2005
    ..abstract_text> ..
  12. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2006
    ....
  13. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2006
    ....
  14. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2007
    ....
  15. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2007
    ....
  16. ENGINEERING MANGANESE METALLOENZYMES
    David W Christianson; Fiscal Year: 2010
    ..Additionally, our studies will enable the design and development of biosensors that may be useful in the early diagnosis of human disease. ..
  17. STRUCTURE/FUNCTION OF EPOXIDE HYDROLASE
    David Christianson; Fiscal Year: 2004
    ..abstract_text> ..
  18. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2004
    ..New inhibitor designs may exhibit enhanced properties such as affinity and membrane permeability, which may facilitate physiological studies of arginase inhibition in the laboratories of our collaborators. ..
  19. STRUCTURE/FUNCTION OF BIOSYNTHETIC ENZYMES
    David Christianson; Fiscal Year: 1999
    ..This work is prerequisite for the structure-based redesign of these enzymes to generate natural and unnatural products of potential medicinal importance. ..
  20. STRUCTURE/FUNCTION OF CARBONIC ANHYDRASE
    David Christianson; Fiscal Year: 2000
    ..The proposed work will answer the question: what structural features constitute an effective catalytic proton shuttle site in an enzyme? ..
  21. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2000
    ..Additionally, using arginase as the prototype, we will continue the development of a structure-based rationale for the design and synthesis and potent metalloenzyme inhibitors that target bimetallic clusters. ..
  22. STRUCTURE/FUNCTION OF BIOSYNTHETIC ENZYMES
    David Christianson; Fiscal Year: 2000
    ..This work is prerequisite for the structure-based redesign of these enzymes to generate natural and unnatural products of potential medicinal importance. ..
  23. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2001
    ..Additionally, using arginase as the prototype, we will continue the development of a structure-based rationale for the design and synthesis and potent metalloenzyme inhibitors that target bimetallic clusters. ..
  24. STRUCTURE/FUNCTION OF BIOSYNTHETIC ENZYMES
    David Christianson; Fiscal Year: 2001
    ..This work is prerequisite for the structure-based redesign of these enzymes to generate natural and unnatural products of potential medicinal importance. ..
  25. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2002
    ..New inhibitor designs may exhibit enhanced properties such as affinity and membrane permeability, which may facilitate physiological studies of arginase inhibition in the laboratories of our collaborators. ..
  26. STRUCTURE/FUNCTION OF EPOXIDE HYDROLASE
    David Christianson; Fiscal Year: 2002
    ..abstract_text> ..
  27. Structure and Function of Biosynthetic Enzymes
    David Christianson; Fiscal Year: 2003
    ..abstract_text> ..
  28. STRUCTURE/FUNCTION OF EPOXIDE HYDROLASE
    David Christianson; Fiscal Year: 2003
    ..abstract_text> ..
  29. ENGINEERING MANGANESE METALLOENZYMES
    David Christianson; Fiscal Year: 2003
    ..New inhibitor designs may exhibit enhanced properties such as affinity and membrane permeability, which may facilitate physiological studies of arginase inhibition in the laboratories of our collaborators. ..