4JMX

Structure of LD transpeptidase LdtMt1 in complex with imipenem

Summary for 4JMX

• Entry DOI: 10.2210/pdb4jmx/pdb
• Related: 4JMN
• Descriptor: Probable L,D-transpeptidase LdtA, (5R)-5-[(1S,2R)-1-formyl-2-hydroxypropyl]-3-[(2-{[(E)-iminomethyl]amino}ethyl)sulfanyl]-4,5-dihydro-1H-pyrrole-2-carbox ylic acid (3 entities in total)
• Functional Keywords: ig-like and beta barrel, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 23941.93

Authors

Correale, S.,Ruggiero, A.,Capparelli, R.,Pedone, E.,Berisio, R. (deposition date: 2013-03-14, release date: 2013-10-23, Last modification date: 2024-10-16)

Primary citation

Correale, S.,Ruggiero, A.,Capparelli, R.,Pedone, E.,Berisio, R.
Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis.
Acta Crystallogr.,Sect.D, 69:1697-1706, 2013

PubMed 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.

PubMed: 23999293
DOI: 10.1107/S0907444913013085

Experimental method

X-RAY DIFFRACTION (2.55 Å)