PDBsum entry 4jmx

Transferase/transferase inhibitor

PDB id: 4jmx

Contents

Protein chain

216 a.a.

Ligands

IM2

Waters ×292

PDB id:

4jmx

Name:

Transferase/transferase inhibitor

Title:

Structure of ld transpeptidase ldtmt1 in complex with imipenem

Structure:

Probable l,d-transpeptidase ldta. Chain: a. Fragment: extracellular domain (unp residues 32-251). Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: ldta, rv0116c. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.55Å R-factor: 0.164 R-free: 0.233

Authors:

S.Correale,A.Ruggiero,R.Capparelli,E.Pedone,R.Berisio

Key ref:

S.Correale et al. (2013). Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr, 69, 1697-1706. PubMed id: 23999293 DOI: 10.1107/S0907444913013085

Date:

14-Mar-13 Release date: 23-Oct-13

Protein chain

O53638  (LDT1_MYCTU) -  L,D-transpeptidase 1 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 251 a.a.

Struc: 216 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.- - ?????

DOI no: 10.1107/S0907444913013085

Acta Crystallogr D Biol Crystallogr 69:1697-1706 (2013)

PubMed id: 23999293

Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis.

S.Correale, A.Ruggiero, R.Capparelli, E.Pedone, R.Berisio.

ABSTRACT

The modelling of peptidoglycan is responsible for key cellular processes in Mycobacterium tuberculosis such as cell growth, division and resuscitation from dormancy. The structure of M. tuberculosis peptidoglycan is atypical since it contains a majority of 3,3 cross-links synthesized by L,D-transpeptidases that replace the 4,3 cross-links formed by the D,D-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate these L,D-transpeptidases and in combination with clavulanic acid are bactericidal against extensively drug-resistant M. tuberculosis. Here, crystal structures of the L,D-transpeptidase LdtMt1 from M. tuberculosis in a ligand-free form and in complex with the carbapenem imipenem are reported. Elucidation of the structural features of LdtMt1 unveils analogies and differences between the two key transpeptidases of M. tuberculosis: LdtMt1 and LdtMt2. In addition, the structure of imipenem-inactivated LdtMt1 provides a detailed structural view of the interactions between a carbapenem drug and LdtMt1. By providing the key interactions in the binding of carbapenem to LdtMt1, this work will facilitate structure-guided discovery of L,D-transpeptidase inhibitors as novel antitubercular agents against drug-resistant M. tuberculosis.