7F71

Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) with peptidoglycan sugar moiety and glutamate

Summary for 7F71

• Entry DOI: 10.2210/pdb7f71/pdb
• Descriptor: L,D-transpeptidase 2, GLYCEROL, GLUTAMIC ACID, ... (5 entities in total)
• Functional Keywords: l, d-transpeptidase, cysteine protease, hydrolase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 79722.61

Authors

Kumar, P.,Lamichhane, G. (deposition date: 2021-06-26, release date: 2022-05-11, Last modification date: 2023-11-29)

Primary citation

Ahmad, N.,Dugad, S.,Chauhan, V.,Ahmed, S.,Sharma, K.,Kachhap, S.,Zaidi, R.,Bishai, W.R.,Lamichhane, G.,Kumar, P.
Allosteric cooperation in beta-lactam binding to a non-classical transpeptidase.
Elife, 11:-, 2022

PubMed Abstract: L,D-transpeptidase function predominates in atypical 3 → 3 transpeptide networking of peptidoglycan (PG) layer . Prior studies of L,D-transpeptidases have identified only the catalytic site that binds to peptide moiety of the PG substrate or β-lactam antibiotics. This insight was leveraged to develop mechanism of its activity and inhibition by β-lactams. Here, we report identification of an allosteric site at a distance of 21 Å from the catalytic site that binds the sugar moiety of PG substrates (hereafter referred to as the S-pocket). This site also binds a second β-lactam molecule and influences binding at the catalytic site. We provide evidence that two β-lactam molecules bind co-operatively to this enzyme, one non-covalently at the S-pocket and one covalently at the catalytic site. This dual β-lactam-binding phenomenon is previously unknown and is an observation that may offer novel approaches for the structure-based design of new drugs against .

PubMed: 35475970
DOI: 10.7554/eLife.73055

Experimental method

X-RAY DIFFRACTION (1.58 Å)