6r72

Crystal structure of BmrA-E504A in an outward-facing conformationCrystal structure of BmrA-E504A in an outward-facing conformation

Structural highlights 6r72 is a 4 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.95Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BMRA_BACSU An efflux transporter able to transport Hoechst 33342, ethidium bromide, doxorubicin and a number of other drugs in vitro into inside out vesicles. The endogenous substrate is unknown. It has been suggested that NBD dimerization induced by ATP-binding causes a large conformational change responsible for substrate translocation (PubMed:18215075). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (Probable). Publication Abstract from PubMed Multidrug ABC transporters translocate drugs across membranes by a mechanism for which the molecular features of drug release are so far unknown. Here, we resolved three ATP-Mg(2+)-bound outward-facing conformations of the Bacillus subtilis (homodimeric) BmrA by x-ray crystallography and single-particle cryo-electron microscopy (EM) in detergent solution, one of them with rhodamine 6G (R6G), a substrate exported by BmrA when overexpressed in B. subtilis. Two R6G molecules bind to the drug-binding cavity at the level of the outer leaflet, between transmembrane (TM) helices 1-2 of one monomer and TM5'-6' of the other. They induce a rearrangement of TM1-2, highlighting a local flexibility that we confirmed by hydrogen/deuterium exchange and molecular dynamics simulations. In the absence of R6G, simulations show a fast postrelease occlusion of the cavity driven by hydrophobicity, while when present, R6G can move within the cavity, maintaining it open. Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter.,Chaptal V, Zampieri V, Wiseman B, Orelle C, Martin J, Nguyen KA, Gobet A, Di Cesare M, Magnard S, Javed W, Eid J, Kilburg A, Peuchmaur M, Marcoux J, Monticelli L, Hogbom M, Schoehn G, Jault JM, Boumendjel A, Falson P Sci Adv. 2022 Jan 28;8(4):eabg9215. doi: 10.1126/sciadv.abg9215. Epub 2022 Jan, 26. PMID:35080979 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6r72, resolution 3.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image