6gv1

Crystal structure of E.coli Multidrug/H+ antiporter MdfA in outward open conformation with bound Fab fragment

spinqualitylabelsall models 6gv1, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gv1 is a 3 chain structure with sequence from Escherichia coli K-12 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.4Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MDFA_ECOLI Efflux pump driven by the proton motive force. Confers resistance to a broad spectrum of chemically unrelated drugs. Confers resistance to a diverse group of cationic or zwitterionic lipophilic compounds such as ethidium bromide, tetraphenylphosphonium, rhodamine, daunomycin, benzalkonium, rifampicin, tetracycline, puromycin, and to chemically unrelated, clinically important antibiotics such as chloramphenicol, erythromycin, and certain aminoglycosides and fluoroquinolones. Overexpression results in isopropyl-beta-D-thiogalactopyranoside (IPTG) exclusion and spectinomycin sensitivity. Transport of neutral substrates is electrogenic, whereas transport of cationic substrates is electroneutral. In addition to its role in multidrug resistance, confers extreme alkaline pH resistance, allowing the growth under conditions that are close to those used normally by alkaliphiles. This activity requires Na(+) or K(+). Publication Abstract from PubMed Multidrug resistance (MDR) poses a major challenge to medicine. A principle cause of MDR is through active efflux by MDR transporters situated in the bacterial membrane. Here we present the crystal structure of the major facilitator superfamily (MFS) drug/H(+) antiporter MdfA from Escherichia coli in an outward open conformation. Comparison with the inward facing (drug binding) state shows that, in addition to the expected change in relative orientations of the N- and C-terminal lobes of the antiporter, the conformation of TM5 is kinked and twisted. In vitro reconstitution experiments demonstrate the importance of selected residues for transport and molecular dynamics simulations are used to gain insights into antiporter switching. With the availability of structures of alternative conformational states, we anticipate that MdfA will serve as a model system for understanding drug efflux in MFS MDR antiporters. Outward open conformation of a Major Facilitator Superfamily multidrug/H(+) antiporter provides insights into switching mechanism.,Nagarathinam K, Nakada-Nakura Y, Parthier C, Terada T, Juge N, Jaenecke F, Liu K, Hotta Y, Miyaji T, Omote H, Iwata S, Nomura N, Stubbs MT, Tanabe M Nat Commun. 2018 Oct 1;9(1):4005. doi: 10.1038/s41467-018-06306-x. PMID:30275448 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA