6EUS
Crystal structure of the outer membrane channel DcaP of Acinetobacter baumannii
Summary for 6EUS
| Entry DOI | 10.2210/pdb6eus/pdb |
| Descriptor | DcaP-like protein (2 entities in total) |
| Functional Keywords | outer membrane protein, acinetobacter baumannii, membrane protein |
| Biological source | Acinetobacter baumannii |
| Total number of polymer chains | 6 |
| Total formula weight | 249151.19 |
| Authors | Zahn, M.,van den Berg, B. (deposition date: 2017-10-31, release date: 2018-11-14, Last modification date: 2024-11-06) |
| Primary citation | Bhamidimarri, S.P.,Zahn, M.,Prajapati, J.D.,Schleberger, C.,Soderholm, S.,Hoover, J.,West, J.,Kleinekathofer, U.,Bumann, D.,Winterhalter, M.,van den Berg, B. A Multidisciplinary Approach toward Identification of Antibiotic Scaffolds for Acinetobacter baumannii. Structure, 27:268-280.e6, 2019 Cited by PubMed Abstract: 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 β-lactamase inhibitor. PubMed: 30554842DOI: 10.1016/j.str.2018.10.021 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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