Covalent inactivation of Mycobacterium thermoresistibile inosine-5'-monophosphate dehydrogenase (IMPDH).
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Trapero, Ana
Pacitto, Angela
Chan, Daniel Shiu-Hin
Abell, Chris https://orcid.org/0000-0001-9174-1987
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
1464-3405
Volume Title
30
Publisher
Elsevier BV
Publisher DOI
Sponsorship
Bill & Melinda Gates Foundation (via Foundation for the National Institutes of Health (FNIH)) (ABELL11HTB0)
European Commission (260872)
Medical Research Council (MR/M026302/1)
European Commission (260872)
Medical Research Council (MR/M026302/1)