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

DOI: 10.1016/j.bmcl.2019.126792 DOI Help

Authors: Ana Trapero (University of Cambridge) , Angela Pacitto (University of Cambridge) , Daniel Shiu-Hin Chan (University of Cambridge) , Chris Abell (University of Cambridge) , Tom L. Blundell (University of Cambridge) , David B. Ascher (University of Cambridge; University of Melbourne) , Anthony G. Coyne (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Bioorganic & Medicinal Chemistry Letters , VOL 30

State: Published (Approved)
Published: January 2020
Diamond Proposal Number(s): 14043

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.

Journal Keywords: IMPDH; GuaB2; Covalent inhibitor; Mycobacterium thermoresistibile IMPDH; 6-Cl-purine ribotide

Diamond Keywords: Enzymes; Bacteria

Subject Areas: Medicine, Biology and Bio-materials, Chemistry


Instruments: I02-Macromolecular Crystallography

Added On: 31/03/2020 11:00

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)