Structural highlights
Function
LDT2_MYCTU Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems.[1]
Publication Abstract from PubMed
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.
Targeting the Mycobacterium tuberculosis transpeptidase LdtMt2 with cysteine-reactive inhibitors including ebselen.,de Munnik M, Lohans CT, Lang PA, Langley GW, Malla TR, Tumber A, Schofield CJ, Brem J Chem Commun (Camb). 2019 Aug 5. doi: 10.1039/c9cc04145a. PMID:31380528[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cordillot M, Dubee V, Triboulet S, Dubost L, Marie A, Hugonnet JE, Arthur M, Mainardi JL. In vitro cross-linking of Mycobacterium tuberculosis peptidoglycan by L,D-transpeptidases and inactivation of these enzymes by carbapenems. Antimicrob Agents Chemother. 2013 Dec;57(12):5940-5. doi: 10.1128/AAC.01663-13., Epub 2013 Sep 16. PMID:24041897 doi:http://dx.doi.org/10.1128/AAC.01663-13
- ↑ de Munnik M, Lohans CT, Lang PA, Langley GW, Malla TR, Tumber A, Schofield CJ, Brem J. Targeting the Mycobacterium tuberculosis transpeptidase LdtMt2 with cysteine-reactive inhibitors including ebselen. Chem Commun (Camb). 2019 Aug 5. doi: 10.1039/c9cc04145a. PMID:31380528 doi:http://dx.doi.org/10.1039/c9cc04145a
