1. Covalent inactivation of Mycobacterium thermoresistibile inosine-5'-monophosphate dehydrogenase (IMPDH)
- Author
-
Tom L. Blundell, Daniel Shiu-Hin Chan, Ana Trapero, David B. Ascher, Angela Pacitto, Chris Abell, and Anthony G. Coyne
- Subjects
Ribonucleotide ,Clinical Biochemistry ,Pharmaceutical Science ,Dehydrogenase ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,01 natural sciences ,Biochemistry ,Residue (chemistry) ,IMP Dehydrogenase ,Bacterial Proteins ,Drug Discovery ,Antimicrobial chemotherapy ,Inosine-5′-monophosphate dehydrogenase ,Enzyme Inhibitors ,Purine metabolism ,Molecular Biology ,Mycobacteriaceae ,Purine Nucleotides ,chemistry.chemical_classification ,Binding Sites ,biology ,010405 organic chemistry ,Organic Chemistry ,biology.organism_classification ,Mycobacterium thermoresistibile ,0104 chemical sciences ,Protein Structure, Tertiary ,010404 medicinal & biomolecular chemistry ,Enzyme ,chemistry ,Drug Design ,biology.protein ,Molecular Medicine - 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.
- Published
- 2019