6ntz

Crystal structure of E. coli PBP5-meropenem

spinqualitylabelsall models 6ntz, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ntz is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: MXR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DACA_ECOLI Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. Publication Abstract from PubMed The bacterial cell wall plays a crucial role in viability and is an important drug target. In Escherichia coli, the peptidoglycan crosslinking reaction to form the cell wall is primarily carried out by penicillin-binding proteins that catalyse D,D-transpeptidase activity. However, an alternate crosslinking mechanism involving the L,D-transpeptidase YcbB can lead to bypass of D,D-transpeptidation and beta-lactam resistance. Here, we show that the crystallographic structure of YcbB consists of a conserved L,D-transpeptidase catalytic domain decorated with a subdomain on the dynamic substrate capping loop, peptidoglycan-binding and large scaffolding domains. Meropenem acylation of YcbB gives insight into the mode of inhibition by carbapenems, the singular antibiotic class with significant activity against L,D-transpeptidases. We also report the structure of PBP5-meropenem to compare interactions mediating inhibition. Additionally, we probe the interaction network of this pathway and assay beta-lactam resistance in vivo. Our results provide structural insights into the mechanism of action and the inhibition of L,D-transpeptidation, and into YcbB-mediated antibiotic resistance. Structural insight into YcbB-mediated beta-lactam resistance in Escherichia coli.,Caveney NA, Caballero G, Voedts H, Niciforovic A, Worrall LJ, Vuckovic M, Fonvielle M, Hugonnet JE, Arthur M, Strynadka NCJ Nat Commun. 2019 Apr 23;10(1):1849. doi: 10.1038/s41467-019-09507-0. PMID:31015395 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carboxypeptidase 3D structures Penicillin-binding protein 3D structures

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