4z7a

Structural and biochemical characterization of a non-functionally redundant M. tuberculosis (3,3) L,D-Transpeptidase, LdtMt5.

spinqualitylabelsall models 4z7a, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4z7a is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Ra. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACE, PEG, PGE, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A5TZL1_MYCTA Publication Abstract from PubMed The final step of peptidoglycan (PG) biosynthesis in bacteria involves crosslinking of peptide side chains. This step in Mycobacterium tuberculosis is catalyzed by L,D- and D,D-transpeptidases that generate 3-->3 and 4-->3 transpeptide linkages, respectively. M. tuberculosis PG is predominantly 3-->3 crosslinked and LdtMt2 is the dominant L,D-transpeptidase. There are four additional sequence paralogs of LdtMt2 encoded by the genome of this pathogen and the reason for this apparent redundancy is unknown. Here, we have studied one of the paralogs, LdtMt5, and found it to be structurally and functionaly distinct. The structures of apo-LdtMt5 and its Meropenem adduct presented here demonstrate that, despite overall architectural similarity to LdtMt2, the LdtMt5 active site has marked differences. The presence of a structurally divergent catalytic site and a proline-rich C-terminal subdomain suggest this protein may have a distinct role in PG metabolism, perhaps involving other cell wall-anchored proteins. Further, M. tuberculosis lacking a functional copy of LdtMt5 displays aberrant growth, and is more susceptible to killing by crystal violet, osmotic shock, and select carbapenem antibiotics. Therefore, we conclude LdtMt5 is not a functionally redundant L,D-transpeptidase, but rather it serves a unique and important role in maintaining the integrity of the M. tuberculosis cell wall. Loss of a functionally and structurally distinct L,D-transpeptidase, LdtMt5, compromises cell wall integrity in Mycobacterium tuberculosis.,Brammer Basta LA, Ghosh A, Pan Y, Jean J, Lloyd EP, Townsend CA, Lamichhane G, Bianchet MA J Biol Chem. 2015 Aug 24. pii: jbc.M115.660753. PMID:26304120 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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