Structural highlights
Function
[LDT2_MYCTO] 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. Is essential for virulence in a mouse model of acute infection.[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
- ↑ Gupta R, Lavollay M, Mainardi JL, Arthur M, Bishai WR, Lamichhane G. The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin. Nat Med. 2010 Apr;16(4):466-9. doi: 10.1038/nm.2120. Epub 2010 Mar 21. PMID:20305661 doi:http://dx.doi.org/10.1038/nm.2120
- ↑ 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
