8BK3

Crystal structure of the transpeptidase LdtMt2 from Mycobacterium tuberculosis in complex with diepoxide ketone 1

Summary for 8BK3

• Entry DOI: 10.2210/pdb8bk3/pdb
• Descriptor: L,D-transpeptidase 2, 1-[(2~{S},3~{R})-3-phenyloxiran-2-yl]ethanone, NITRATE ION, ... (7 entities in total)
• Functional Keywords: l, d-transpeptidase, ldtmt2, inhibitor, covalent, antimicrobial protein
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 76738.92

Authors

de Munnik, M.,Schofield, C.J. (deposition date: 2022-11-08, release date: 2023-11-22, Last modification date: 2024-10-16)

Primary citation

de Munnik, M.,Lithgow, J.,Brewitz, L.,Christensen, K.E.,Bates, R.H.,Rodriguez-Miquel, B.,Schofield, C.J.
alpha beta , alpha ' beta '-Diepoxyketones are mechanism-based inhibitors of nucleophilic cysteine enzymes.
Chem.Commun.(Camb.), 59:12859-12862, 2023

PubMed Abstract: Epoxides are an established class of electrophilic alkylating agents that react with nucleophilic protein residues. We report αβ,α'β'-diepoxyketones (DEKs) as a new type of mechanism-based inhibitors of nucleophilic cysteine enzymes. Studies with the L,D-transpeptidase Ldt from and the main protease from SARS-CoV-2 (M) reveal that following epoxide ring opening by a nucleophilic cysteine, further reactions can occur, leading to irreversible alkylation.

PubMed: 37815791
DOI: 10.1039/d3cc02932h

Experimental method

X-RAY DIFFRACTION (2.15 Å)