Structural highlights
5m2h is a 2 chain structure with sequence from Amycolatopsis orientalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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Method: | X-ray diffraction, Resolution 0.95Å |
Ligands: | , , , , , , , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and we show that the activity of other glycopeptide antibiotics with this feature can also be similarly augmented by Zn(II). Construction and analysis of a model strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis during normal growth supports the hypothesis that Zn(II) mediated vancomycin polymerization enhances the binding affinity towards these precursors.
Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria.,Zarkan A, Macklyne HR, Chirgadze DY, Bond AD, Hesketh AR, Hong HJ Sci Rep. 2017 Jul 7;7(1):4893. doi: 10.1038/s41598-017-04868-2. PMID:28687742[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zarkan A, Macklyne HR, Chirgadze DY, Bond AD, Hesketh AR, Hong HJ. Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria. Sci Rep. 2017 Jul 7;7(1):4893. doi: 10.1038/s41598-017-04868-2. PMID:28687742 doi:http://dx.doi.org/10.1038/s41598-017-04868-2