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Crystals, molecular complexes, and methods of developing lead compounds for inhibitors of bacterial IMPDH

Patent ·
OSTI ID:1531490
; ; ; ;

The present invention relates to a data storage medium encoded with the structural coordinates of crystallized molecules and molecular complexes which comprise the active site binding pockets of bacterial IMPDH. Such data storage material is capable of displaying such molecules and molecular complexes, or their structural homologues, as a graphical three-dimensional representation on a computer screen. This invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. In addition, this invention relates to methods of using the structure coordinates to screen and design compounds, including inhibitory compounds, that bind to IMPDH or homologues thereof. This invention also relates to molecules and molecular complexes that comprise the active site binding pockets of IMPDH or close structural homologues of the active site binding pockets. This invention also relates to compounds and pharmaceutical compositions which are inhibitors of bacterial IMPDH.

Research Organization:
Univ. of Chicago, Chicago, IL (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
W-31109-ENG-38
Assignee:
The University of Chicago (Chicago, IL)
Patent Number(s):
6,826,488
Application Number:
09/533,466
OSTI ID:
1531490
Country of Publication:
United States
Language:
English

References (32)

Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features journal December 1983
Clinical pharmacokinetic study of tiazofurin administered as a 1-hour infusion journal May 1992
Cognitive features of continuous antigenic determinants journal February 1988
Torsion angle dynamics: Reduced variable conformational sampling enhances crystallographic structure refinement journal August 1994
Probing the Mechanism of Inosine Monophosphate Dehydrogenase with Kinetic Isotope Effects and NMR Determination of the Hydride Transfer Stereospecificity journal December 1997
Structural Features can be Unconserved in Proteins with Similar Folds journal December 1994
Recombinant human inosine monophosphate dehydrogenase type I and type II proteins journal May 1995
Cloning, sequence analysis and expression of the group A streptococcal guaB gene encoding inosine monophosphate dehydrogenase journal January 1995
Cloning, characterization and sequence comparison of the gene coding for IMP dehydrogenase from Pyrococcus furiosus journal January 1996
Cloning and characterization of the gene encoding IMP dehydrogenase from Arabidopsis thaliana journal January 1996
[17] Charge-coupled device-based area detectors book January 1997
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997
[31] Treatment of multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement book January 1997
[33] AMoRe: An automated molecular replacement program package book December 1996
Structure and Mechanism of Inosine Monophosphate Dehydrogenase in Complex with the Immunosuppressant Mycophenolic Acid journal June 1996
The structure of a domain common to archaebacteria and the homocystinuria disease protein journal January 1997
Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus journal October 1995
Human IMP Dehydrogenase Catalyzes the Dehalogenation of 2-Fluoro- and 2-Chloroinosine 5'-Monophosphate in the Absence of NAD journal February 1994
Probing the Active Site of Human IMP Dehydrogenase Using Halogenated Purine Riboside 5'-Monophosphates and Covalent Modification Reagents journal February 1994
Inactivation of Inosine 5‘-Monophosphate Dehydrogenase by the Antiviral Agent 5-Ethynyl-1-β- d -Ribofuranosylimidazole-4-Carboxamide 5‘-Monophosphate † journal January 1996
Inhibition of IMPDH by Mycophenolic Acid:  Dissection of Forward and Reverse Pathways Using Capillary Electrophoresis journal January 1996
Crystal Structure of Tritrichomonas foetus Inosine-5‘-monophosphate Dehydrogenase and the Enzyme−Product Complex † journal September 1997
The Roles of Conserved Carboxylate Residues in IMP Dehydrogenase and Identification of a Transition State Analog † journal October 1997
Characteristics and Crystal Structure of Bacterial Inosine-5‘-monophosphate Dehydrogenase † , ‡ journal April 1999
Trapping of an IMP Dehydrogenase−Substrate Covalent Intermediate by Mycophenolic Acid journal January 1996
A Controlled Trial of Aerosolized Ribavirin in Infants Receiving Mechanical Ventilation for Severe Respiratory Syncytial Virus Infection journal July 1991
Conformational Changes and Stabilization of Inosine 5′-Monophosphate Dehydrogenase Associated with Ligand Binding and Inhibition by Mycophenolic Acid journal August 1996
Expression, Purification, and Characterization of Inosine 5′-Monophosphate Dehydrogenase from Borrelia burgdorferi journal August 1997
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination journal September 1998
Incorporation of Prior Phase Information Strengthens Maximum-Likelihood Structure Refinement journal November 1998
Determination of macromolecular structures from anomalous diffraction of synchrotron radiation journal October 1991
Expression of IMP dehydrogenase in differentiating HL-60 cells journal February 1990

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