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Covalent inactivation of Mycobacterium thermoresistibile inosine-5'-monophosphate dehydrogenase (IMPDH).

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Trapero, Ana 
Pacitto, Angela 
Chan, Daniel Shiu-Hin 
Blundell, Tom L 

Abstract

Inosine-5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme involved in nucleotide biosynthesis. Because of its critical role in purine biosynthesis, IMPDH is a drug design target for immunosuppressive, anticancer, antiviral and antimicrobial chemotherapy. In this study, we use mass spectrometry and X-ray crystallography to show that the inhibitor 6-Cl-purine ribotide forms a covalent adduct with the Cys-341 residue of Mycobacterium thermoresistibile IMPDH.

Description

Keywords

6-Cl-purine ribotide, Covalent inhibitor, GuaB2, IMPDH, Mycobacterium thermoresistibile IMPDH, Bacterial Proteins, Binding Sites, Crystallography, X-Ray, Drug Design, Enzyme Inhibitors, IMP Dehydrogenase, Molecular Dynamics Simulation, Mycobacteriaceae, Protein Structure, Tertiary, Purine Nucleotides

Journal Title

Bioorg Med Chem Lett

Conference Name

Journal ISSN

0960-894X
1464-3405

Volume Title

30

Publisher

Elsevier BV
Sponsorship
Bill & Melinda Gates Foundation (via Foundation for the National Institutes of Health (FNIH)) (ABELL11HTB0)
European Commission (260872)
Medical Research Council (MR/M026302/1)