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Targeting the Mycobacterium tuberculosis transpeptidase Ldt<sub>Mt2</sub> with cysteine-reactive inhibitors including ebselen.

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.

SUBMITTER: de Munnik M 

PROVIDER: S-EPMC6984337 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Targeting the Mycobacterium tuberculosis transpeptidase Ldt&lt;sub&gt;Mt2&lt;/sub&gt; with cysteine-reactive inhibitors including ebselen.

de Munnik Mariska M   Lohans Christopher T CT   Lang Pauline A PA   Langley Gareth W GW   Malla Tika R TR   Tumber Anthony A   Schofield Christopher J CJ   Brem Jürgen J  

Chemical communications (Cambridge, England) 20190801 69

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. ...[more]

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