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PDBsum entry 4jmx
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Transferase/transferase inhibitor
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PDB id
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4jmx
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References listed in PDB file
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Key reference
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Title
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Structures of free and inhibited forms of the l,D-Transpeptidase ldtmt1 from mycobacterium tuberculosis.
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Authors
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S.Correale,
A.Ruggiero,
R.Capparelli,
E.Pedone,
R.Berisio.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2013,
69,
1697-1706.
[DOI no: ]
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PubMed id
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Abstract
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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.
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