Structure of Ldt_Mt2, anL,D-transpeptidase fromMycobacterium tuberculosis

Abstract

The crystal structures of two fragments of the l,d-transpeptidase from M. tuberculosis have been determined at 1.45 and 1.86 Å resolution. The extramembrane part of this enzyme consists of three domains: two domains related to the immunoglobulin fold and a catalytic domain belonging to the ErfK/YbiS/YhnG family at the C-terminus.

Nonclassical Transpeptidases of Mycobacterium tuberculosis Alter Cell Size, Morphology, the Cytosolic Matrix, Protein Localization, Virulence, and Resistance to β-Lactams

“…The crystal structure of Ldt Mt2 was recently reported by four independent groups (19)(20)(21)(22). These studies also report molecular interactions with the substrate and the carbapenem class of drugs and the mechanism of catalysis by Ldt Mt2 .…”

“…While biochemical properties and the contribution of Ldt Mt2 to the physiology of M. tuberculosis have been reported (16,(19)(20)(21)(22), studies of Ldt Mt1 have been limited to biochemical characterization (6,23). In this study, for the first time, we have generated and studied M. tuberculosis strains lacking Ldt Mt1 and both Ldt Mt1 and Ldt Mt2 and describe the cellular phenotypes associated with the loss of these L,D-transpeptidases.…”

“…Despite the significance of D,D-transpeptidases, which serve as targets to the most widely used class of antibiotics, the study of the relevance of L,D-transpeptidases to the physiology of the cell and susceptibility to drugs has only recently begun. Within 6 months following the first report describing the crystal structure and mechanism of L,Dtranspeptidation by Ldt Mt2 (19), four additional reports describing structural details of L,D-transpeptidases of M. tuberculosis were published (20)(21)(22)(23).…”

Targeting the cell wall ofMycobacterium tuberculosis: a molecular modeling investigation of the interaction of imipenem and meropenem withL,D-transpeptidase 2

“…The 3,3-transpeptidase has since then attracted the attention of several researchers. (De & McIntosh 2012;Dubee et al 2012;Erdemli et al 2012;Lecoq et al 2012;Both et al 2013;Cordillot et al 2013;Correale, Ruggiero, Capparelli, Pedone & Berisio 2013;Kim et al 2013;Lecoq et al 2013;Li et al 2013;Triboulet et al 2013;Sanders, Wright & Pavelka 2014;Schoonmaker et al 2014) We have determined the experimental binding free energies of imipenem and meropenem (see Figure 1) to ex-Ldt Mtb2 utilizing isothermal titration calorimetry (ITC) experiments. (Erdemli et al 2012) Figure 1.…”

Peptidoglycan Remodeling by the Coordinated Action of Multispecific Enzymes

“…59 The crystal structure of the C-terminal domain of YkuD from B. subtilis and the catalytic domain of Ldt fm of E. faecium were described in 2006 8,9 and the structures of Ldts Mt1 and Mt2 from Mycobacterium tuberculosis have been reported recently. 13,21,23,43 In this work, a reaction mechanism was proposed in which both the acyl-acceptor and the acyl-donor substrates enter the catalytic site through the same entry. All enzymes so far described present similar two-domain architectures and highly conserved catalytic domains, being only slightly distinct at their N-terminal domain.…”