5b1o

DHp domain structure of EnvZ P248A mutant

spinqualitylabelsall models 5b1o, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5b1o is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENVZ_ECOLI Member of the two-component regulatory system EnvZ/OmpR involved in the regulation of osmoregulation (genes ompF and ompC). EnvZ functions as a membrane-associated protein kinase that phosphorylates OmpR in response to environmental signals. Publication Abstract from PubMed Two-component signal transduction systems (TCSs), composed of a histidine kinase sensor (HK) and its cognate response regulator, sense and respond to environmental changes and are related to the virulence of pathogens. TCSs are potential targets for alternative antibiotics and anti-virulence agents. Here we found that waldiomycin, an angucycline antibiotic that inhibits a growth essential HK, WalK, in Gram-positive bacteria, also inhibits several class I HKs from the Gram-negative Escherichia coli. NMR analyses and site-directed mutagenesis studies using the osmo-sensing EnvZ, a prototypical HK of E. coli, showed that waldiomycin directly binds to both H-box and X-region, which are the two conserved regions in the dimerization-inducing and histidine-containing phosphotransfer (DHp) domain of HKs. Waldiomycin inhibits phosphorylation of the conserved histidine in the H-box. Analysis of waldiomycin derivatives suggests that the angucyclic ring, situated near the H-box in the waldiomycin-EnvZ DHp domain complex model, is responsible for the inhibitory activity. We demonstrate that waldiomycin is an HK inhibitor binding to the H-box region and has the potential of inhibiting a broad spectrum of HKs. Angucycline antibiotic waldiomycin recognizes common structural motif conserved in bacterial histidine kinases.,Eguchi Y, Okajima T, Tochio N, Inukai Y, Shimizu R, Ueda S, Shinya S, Kigawa T, Fukamizo T, Igarashi M, Utsumi R J Antibiot (Tokyo). 2017 Mar;70(3):251-258. doi: 10.1038/ja.2016.151. Epub 2016, Dec 21. PMID:27999439 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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