9gsj | pdb_00009gsj

BmrA E504A in complex with Hoechst33342

spinqualitylabelsall models 9gsj, resolution 3.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9gsj is a 2 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: Electron Microscopy, Resolution 3.6Å Ligands: HT1 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 harness the energy of ATP binding and hydrolysis to translocate substrates out of the cell and detoxify them. While this involves a well-accepted alternating access mechanism, molecular details of this interplay are still elusive. Rhodamine6G binding on a catalytic inactive mutant of the homodimeric multidrug ABC transporter BmrA triggers a cooperative binding of ATP on the two identical nucleotide-binding-sites, otherwise michaelian. Here, we investigate this asymmetric behavior via a structural-enzymology approach, solving cryoEM structures of BmrA at defined ATP ratios, highlighting the plasticity of BmrA as it undergoes the transition from inward to outward facing conformations. Analysis of continuous heterogeneity within cryoEM data and structural dynamics, reveals that Rhodamine6G narrows the conformational spectrum explored by the nucleotide-binding domains. We observe the same behavior for the other drug Hoechst33342. Following on these findings, the effect of drug-binding showed an ATPase stimulation and a maximal transport activity of the wild-type protein at the concentration-range where the cooperative transition occurs. Altogether, these findings provide a description of the influence of drug binding on the ATP-binding sites through a change in conformational dynamics. Rhodamine6G and Hoechst33342 narrow BmrA conformational spectrum for a more efficient use of ATP.,Gobet A, Moissonnier L, Zarkadas E, Magnard S, Bettler E, Martin J, Terreux R, Schoehn G, Orelle C, Jault JM, Falson P, Chaptal V Nat Commun. 2025 Feb 18;16(1):1745. doi: 10.1038/s41467-025-56849-z. PMID:39966360 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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