6eus

Crystal structure of the outer membrane channel DcaP of Acinetobacter baumannii

spinqualitylabelsall models 6eus, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6eus is a 6 chain structure with sequence from Acinetobacter baumannii. 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: MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0B9X9I7_ACIBA Publication Abstract from PubMed Research efforts to discover potential new antibiotics for Gram-negative bacteria suffer from high attrition rates due to the synergistic action of efflux systems and the limited permeability of the outer membrane (OM). One strategy to overcome the OM permeability barrier is to identify small molecules that are natural substrates for abundant OM channels and use such compounds as scaffolds for the design of efficiently permeating antibacterials. Here we present a multidisciplinary approach to identify such potential small-molecule scaffolds. Focusing on the pathogenic bacterium Acinetobacter baumannii, we use OM proteomics to identify DcaP as the most abundant channel during infection in rodents. The X-ray crystal structure of DcaP reveals a trimeric, porin-like structure and suggests that dicarboxylic acids are potential transport substrates. Electrophysiological experiments and all-atom molecular dynamics simulations confirm this notion and provide atomistic information on likely permeation pathways and energy barriers for several small molecules, including a clinically relevant beta-lactamase inhibitor. A Multidisciplinary Approach toward Identification of Antibiotic Scaffolds for Acinetobacter baumannii.,Bhamidimarri SP, Zahn M, Prajapati JD, Schleberger C, Soderholm S, Hoover J, West J, Kleinekathofer U, Bumann D, Winterhalter M, van den Berg B Structure. 2019 Feb 5;27(2):268-280.e6. doi: 10.1016/j.str.2018.10.021. Epub 2018, Dec 13. PMID:30554842 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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