6hai | pdb_00006hai

AlbAM131A mutant in complex with albicidin , albicidin resistance protein

spinqualitylabelsall models 6hai, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hai is a 2 chain structure with sequence from "bacillus_oxytocus_perniciosus"_flugge_1886 "bacillus oxytocus perniciosus" flugge 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FWW, SO4 Gene: albA ("Bacillus oxytocus perniciosus" Flugge 1886) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed To combat the rise of antimicrobial resistance, the discovery of new antibiotics is paramount. Albicidin and cystobactamid are related natural product antibiotics with potent activity against Gram-positive and, crucially, Gram-negative pathogens. AlbA has been reported to neutralize albicidin by binding it with nanomolar affinity. To understand this potential resistance mechanism, we determined structures of AlbA and its complex with albicidin. The structures revealed AlbA to be comprised of two domains, each unexpectedly resembling the multiantibiotic neutralizing protein TipA. Binding of the long albicidin molecule was shared pseudosymmetrically between the two domains. The structure also revealed an unexpected chemical modification of albicidin, which we demonstrate to be promoted by AlbA, and to reduce albicidin potency; we propose a mechanism for this reaction. Overall, our findings suggest that AlbA arose through internal duplication in an ancient TipA-like gene, leading to a new binding scaffold adapted to the sequestration of long-chain antibiotics. Adaptation of a Bacterial Multidrug Resistance System Revealed by the Structure and Function of AlbA.,Sikandar A, Cirnski K, Testolin G, Volz C, Bronstrup M, Kalinina OV, Muller R, Koehnke J J Am Chem Soc. 2018 Dec 5;140(48):16641-16649. doi: 10.1021/jacs.8b08895. Epub, 2018 Nov 27. PMID:30422653 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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