Targeting the Mycobacterium tuberculosis transpeptidase Ldt<sub>Mt2</sub> with cysteine-reactive inhibitors including ebselen
de Munnik M , Lohans CT , Lang PA , Langley GW , Malla TR , Tumber A , Schofield CJ , Brem J
Chemical communications (Cambridge, England) · 2019-08
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
- Humans
- Mycobacterium tuberculosis
- Tuberculosis
- Benzene Derivatives
- Organoselenium Compounds
- Cysteine
- Azoles
- Peptidyl Transferases
- Enzyme Inhibitors
- Antitubercular Agents
- Isoindoles
- Molecular Docking Simulation