Targeting the <i>Mycobacterium tuberculosis</i> transpeptidase Ldt<sub>Mt2</sub> with cysteine-reactive inhibitors including ebselen
Mariska de Munnik, Christopher T. Lohans, Pauline A. Lang, Gareth W. Langley, Tika R. Malla, Anthony Tumber, Christopher J. Schofield, Jürgen Brem
Chemical Communications · 2019-01
Abstract
The l,d-transpeptidases (Ldts) are promising antibiotic targets for treating tuberculosis. We report screening of cysteine-reactive inhibitors against LdtMt2 from Mycobacterium tuberculosis. Structural studies on LdtMt2 with potent inhibitor ebselen reveal opening of the benzisoselenazolone ring by a nucleophilic cysteine, forming a complex involving extensive hydrophobic interactions with a substrate-binding loop.
MeSH terms
- Ebselen
- Cysteine
- Mycobacterium tuberculosis
- Chemistry
- Tuberculosis
- Nucleophile
- Microbiology
- Biochemistry
- Enzyme