6bpl

E. coli MsbA in complex with LPS and inhibitor G907

spinqualitylabelsall models 6bpl, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bpl is a 2 chain structure with sequence from Escherichia coli CFT073. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.908Å Ligands: 3PE, AU7, DAO, DPO, FTT, GCS, GLC, GMH, KDO, MYR, PA1, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MSBA_ECOL6 Involved in lipid A export and possibly also in glycerophospholipid export and for biogenesis of the outer membrane. Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation. Publication Abstract from PubMed The movement of core-lipopolysaccharide across the inner membrane of Gram-negative bacteria is catalysed by an essential ATP-binding cassette transporter, MsbA. Recent structures of MsbA and related transporters have provided insights into the molecular basis of active lipid transport; however, structural information about their pharmacological modulation remains limited. Here we report the 2.9 A resolution structure of MsbA in complex with G907, a selective small-molecule antagonist with bactericidal activity, revealing an unprecedented mechanism of ABC transporter inhibition. G907 traps MsbA in an inward-facing, lipopolysaccharide-bound conformation by wedging into an architecturally conserved transmembrane pocket. A second allosteric mechanism of antagonism occurs through structural and functional uncoupling of the nucleotide-binding domains. This study establishes a framework for the selective modulation of ABC transporters and provides rational avenues for the design of new antibiotics and other therapeutics targeting this protein family. Structural basis for dual-mode inhibition of the ABC transporter MsbA.,Ho H, Miu A, Alexander MK, Garcia NK, Oh A, Zilberleyb I, Reichelt M, Austin CD, Tam C, Shriver S, Hu H, Labadie SS, Liang J, Wang L, Wang J, Lu Y, Purkey HE, Quinn J, Franke Y, Clark K, Beresini MH, Tan MW, Sellers BD, Maurer T, Koehler MFT, Wecksler AT, Kiefer JR, Verma V, Xu Y, Nishiyama M, Payandeh J, Koth CM Nature. 2018 May 2. pii: 10.1038/s41586-018-0083-5. doi:, 10.1038/s41586-018-0083-5. PMID:29720648 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA