Research Topics
| V CodySummaryAffiliation: University at Buffalo Country: USA Publications
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Publications
Structure-activity correlations of variant forms of the B pentamer of Escherichia coli type II heat-labile enterotoxin LT-IIb with Toll-like receptor 2 bindingVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 68:1604-12. 2012..These data are consistent with the lack of binding of the LT-IIb-B(5)(T13I) variant to GD1a ganglioside...
Structural analysis of Pneumocystis carinii dihydrofolate reductase complexed with NADPH and 2,4-diamino-6-[2-(5-carboxypent-1-yn-1-yl)-5-methoxybenzyl]-5-methylpyrido[2,3-d]pyrimidineVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA
Acta Crystallogr Sect F Struct Biol Cryst Commun 68:418-23. 2012..The greater selectivity for pcDHFR compared with mammalian DHFR of these inhibitors is also influenced by the enhanced hydrophobic interactions of the side-chain methylene atoms with Phe69 of pcDHFR compared with Asn64 of mammalian DHFR...
Purification and characterization of human-derived Pneumocystis jirovecii dihydrofolate reductase expressed in Sf21 insect cells and in Escherichia coliVivian Cody
Department of Structural Biology, Hauptman Woodward Medical Research Institute, 73 High St Buffalo, NY 14203, USA
Protein Expr Purif 40:417-23. 2005..These protocols now make it possible to facilitate screening of antifolates with selectivity for human-derived pDHFR and to determine its three-dimensional structure...
New insights into DHFR interactions: analysis of Pneumocystis carinii and mouse DHFR complexes with NADPH and two highly potent 5-(omega-carboxy(alkyloxy) trimethoprim derivatives reveals conformational correlations with activity and novel parallel ring sVivian Cody
Department of Structural Biology, Hauptman Woodward Medical Research Institute, Buffalo, New York 14203, USA
Proteins 65:959-69. 2006..A unique His174-His187 parallel ring stacking interaction was also observed only in the structure of pcDHFR. These ring stacking interactions are rarely found in any other protein families and may serve to enhance protein stability...
Molecular modeling of the thyroid hormone interactions with alpha v beta 3 integrinVivian Cody
Hauptman Woodward Medical Research Institute, 700 Ellicott St, Buffalo, NY 14203, USA
Steroids 72:165-70. 2007..In this model, most of the hormone interactions are with betaA domain of the integrin. Mutagenic studies can be carried out to validate the role of these residues in directing hormone interactions...
Recombinant bovine dihydrofolate reductase produced by mutagenesis and nested PCR of murine dihydrofolate reductase cDNAVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, Buffalo, NY 14203, USA
Protein Expr Purif 62:104-10. 2008..Expression of the bovine DHFR cDNA in bacterial cells produced a stable recombinant protein with high enzymatic activity and kinetic properties similar to those previously reported for the native protein...
Structural analysis of a holoenzyme complex of mouse dihydrofolate reductase with NADPH and a ternary complex with the potent and selective inhibitor 2,4-diamino-6-(2'-hydroxydibenz[b,f]azepin-5-yl)methylpteridineVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 64:977-84. 2008..6 A compared with pcDHFR ternary complexes. These data are consistent with the greater inhibitory potency against pcDHFR...
Correlations of inhibitor kinetics for Pneumocystis jirovecii and human dihydrofolate reductase with structural data for human active site mutant enzyme complexesVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, New York 14203, USA
Biochemistry 48:1702-11. 2009..This insight will help in the design of more selective inhibitors that target these opportunistic pathogens...
The Z isomer of 2,4-diaminofuro[2,3-d]pyrimidine antifolate promotes unusual crystal packing in a human dihydrofolate reductase ternary complexVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, Buffalo, NY 14203, USA
Acta Crystallogr Sect F Struct Biol Cryst Commun 65:762-6. 2009..As a result, the conformations of Phe31 and Gln35 shift with respect to those observed in the structure of mouse DHFR bound to Z1, which crystallizes in the monoclinic space group P2(1) and shows that Gln35 interacts with Arg70...
Preferential selection of isomer binding from chiral mixtures: alternate binding modes observed for the E and Z isomers of a series of 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines as ternary complexes with NADPH and human dihydrofolate reductaseVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 66:1271-7. 2010..The alternative binding modes observed for the furopyrimidine ring in these E/Z isomers suggest that new templates can be designed to probe these binding regions of the DHFR active site...
Structural analysis of Pneumocystis carinii and human DHFR complexes with NADPH and a series of five potent 6-[5'-(ω-carboxyalkoxy)benzyl]pyrido[2,3-d]pyrimidine derivativesVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, Buffalo, New York 14203, USA
Acta Crystallogr D Biol Crystallogr 67:1-7. 2011....
Crystallographic analysis reveals a novel second binding site for trimethoprim in active site double mutants of human dihydrofolate reductaseVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 700 Ellicott St Buffalo, NY 14203, USA
J Struct Biol 176:52-9. 2011..These results suggest that active site residues 35 and 64 play key roles in determining selectivity for pneumocystis DHFR, but that other residues contribute to the unique binding of inhibitors to these enzymes...
Structural analysis of human dihydrofolate reductase as a binary complex with the potent and selective inhibitor 2,4-diamino-6-{2'-O-(3-carboxypropyl)oxydibenz[b,f]-azepin-5-yl}methylpteridine reveals an unusual binding modeVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 67:875-80. 2011..These data suggest that the greater inhibitory potency of PT684 against pcDHFR is consistent with the larger active-site volume of pcDHFR and the predicted interactions of the carboxylate side chain with Arg75...
Understanding the role of Leu22 variants in methotrexate resistance: comparison of wild-type and Leu22Arg variant mouse and human dihydrofolate reductase ternary crystal complexes with methotrexate and NADPHVivian Cody
Hauptman Woodward Medical Research Institute, 73 High Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 61:147-55. 2005....
Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523V Cody
Hauptman Woodward Medical Research Institute, Inc, Buffalo, New York 14203, USA
Biochemistry 36:13897-903. 1997..However, the crystallographic data reveal more discretely occupied positions than can be interpreted from the solution data. These results suggest that crystal packing interactions may influence their stability...
Comparison of ternary crystal complexes of F31 variants of human dihydrofolate reductase with NADPH and a classical antitumor furopyrimidineV Cody
Hauptman Woodward Medical Research Institute, Inc, NY 14203, USA
Anticancer Drug Des 13:307-15. 1998..For the design of antitumor agents related to MTXO, increasing the bridge of MTXO from two to three or four atoms should provide increased DHFR inhibitory potency and antitumor activity...
Ligand-induced conformational changes in the crystal structures of Pneumocystis carinii dihydrofolate reductase complexes with folate and NADP+V Cody
Hauptman Woodward Medical Research Institute, Inc, Buffalo, New York, USA
Biochemistry 38:4303-12. 1999....
Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling studies on the Pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolateV Cody
Hauptman Woodward Medical Research Institute, Inc, Buffalo, New York 14203, USA
Biochemistry 39:3556-64. 2000..Further modification of the acetyloxy region of TAB could increase its potency and selectivity for pcDHFR...
Structure-based enzyme inhibitor design: modeling studies and crystal structure analysis of Pneumocystis carinii dihydrofolate reductase ternary complex with PT653 and NADPHVivian Cody
Hauptman Woodward Medical Research Institute, Inc, 73 High Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 58:946-54. 2002..Homology-modeling studies of the tgDHFR structure suggest that differences in ligand-binding orientation and enzyme sequence could influence the enhanced selectivity of PT653 for tgDHFR...
Analysis of quinazoline and pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductaseVivian Cody
Hauptman Woodward Medical Research Institute, Inc, 73 High Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 58:1393-9. 2002..These data suggest that the loss of hydrogen-bonding interactions with N8 is more important to potency than the interactions of the methoxybenzyl substituents...
Mechanisms of molecular recognition: crystal structure analysis of human and rat transthyretin inhibitor complexesVivian Cody
Hauptman Woodward Medical Research Institute, Buffalo, NY 14203, USA
Clin Chem Lab Med 40:1237-43. 2002..These data highlight the importance of hydrogen bonding with Lys-15 and Ser-117 and provide insight into ligand binding affinity and negative cooperativity...
Analysis of two polymorphic forms of a pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolate binary complex with human dihydrofolate reductaseVivian Cody
Hauptman Woodward Medical Research Institute Inc, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 59:654-61. 2003..This also influences the conformation of the methoxybenzyl ring, moving it away from a trans position and placing the 5'-methoxy group deeper within the hydrophobic pocket made by Leu60, Pro61 and Asn64 of the hDHFR active site...
Analysis of three crystal structure determinations of a 5-methyl-6-N-methylanilino pyridopyrimidine antifolate complex with human dihydrofolate reductaseVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute Inc, 73 High Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 59:1603-9. 2003....
Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistryVivian Cody
Structural Biology Department, Hauptman Woodward Medical Research Institute, 73 High Street, Buffalo, NY 14203, USA
Acta Crystallogr D Biol Crystallogr 60:646-55. 2004....
Structure of the insecticidal bacterial delta-endotoxin Cry3Bb1 of Bacillus thuringiensisN Galitsky
Hauptman-Woodward Research Institute, Inc, 73 High Street, Buffalo, NY 14203-1196, USA
Acta Crystallogr D Biol Crystallogr 57:1101-9. 2001..These changes can be implicated in the selectivity differences noted for these two delta-endotoxins...
Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzymeY Wang
Structural Biology Department, Hauptman Woodward Medical Research Institute, Buffalo, New York 14203, USA
Antimicrob Agents Chemother 45:2517-23. 2001..However, variations between rat and human DHFR enzymes, coupled with unique features in the inhibitors, could lead to the observed differences in enzyme sensitivity and selectivity...
Sliding clamp-DNA interactions are required for viability and contribute to DNA polymerase management in Escherichia coliJustin M H Heltzel
Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA
J Mol Biol 387:74-91. 2009..Taken together, these results support a model in which a sophisticated combination of competitive clamp-DNA, clamp-partner, and partner-DNA interactions serve to manage the actions of the different E. coli Pols in vivo...
Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolutionPiotr Neumann
Institute of Chemistry, N Copernicus University, Gagarina 7, 87 100 Torun, Poland
Acta Crystallogr D Biol Crystallogr 61:1313-9. 2005..Such interactions of a thyroxine-analogue ligand bound in the reverse mode have never been observed in TTR complexes previously...
Designing protein dimerizers: the importance of ligand conformational equilibriaJonathan C T Carlson
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA
J Am Chem Soc 125:1501-7. 2003..Consequently, the secondary structure of this minimal foldamer regulates its ability to dimerize dihydrofolate reductase in solution, providing insight into the complex energy landscape of induced dimerization...
Haloperidol: towards further understanding of the structural contributions of its pharmacophoric elements at D2-like receptorsDonald M N Sikazwe
College of Pharmacy and Pharmaceutical Sciences, Florida A and M University, Tallahassee, FL 32307, USA
Bioorg Med Chem Lett 14:5739-42. 2004..It also became clear that shortening the butyrophenone chain not only reduces binding affinity at the DA receptors but eliminates subtype selectivity...
Membrane receptors mediating thyroid hormone actionPaul J Davis
Ordway Research Institute Inc, Albany, NY 12208, USA
Trends Endocrinol Metab 16:429-35. 2005..Examples of such modifications are provided...
Research Grants
- Structural Studies of AIDS-Responsive DrugsVivian Cody; Fiscal Year: 2007..These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilities in the structure-based correlations to help design novel pjDHFR inhibitors. ..
- STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGSVivian Cody; Fiscal Year: 2004..Dr. Sherry Queener, Indiana University, will measure inhibitory activity of selected antifolates. ..
- STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGSVivian Cody; Fiscal Year: 2000..Dr. Sherry Queener, Indiana University, will supply samples of pcDHFR and measure the pc activity of new antifolates. ..
- Structural Studies of AIDS-Responsive DrugsVivian Cody; Fiscal Year: 2010..These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilitiesin the structure-based correlations to help design novel pjDHFRinhibitors. ..
