6BPP

E. coli MsbA in complex with LPS and inhibitor G092

6BPP の概要

• エントリーDOI: 10.2210/pdb6bpp/pdb
• 分子名称: Lipid A export ATP-binding/permease protein MsbA, alpha-D-glucopyranose-(1-3)-[alpha-D-glucopyranose-(1-6)]alpha-D-glucopyranose-(1-3)-[L-glycero-alpha-D-manno-heptopyranose-(1-7)]L-glycero-alpha-D-manno-heptopyranose-(1-3)-L-glycero-alpha-D-manno-heptopyranose-(1-5)-[3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-4)]3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-6)-2-amino-2-deoxy-beta-D-glucopyranose-(1-6)-2-amino-2-deoxy-alpha-D-glucopyranose, (2E)-3-{6-[(1S)-1-(3-amino-2,6-dichlorophenyl)ethoxy]-4-cyclopropylquinolin-3-yl}prop-2-enoic acid, ... (8 entities in total)
• 機能のキーワード: abc transporter, inhibitor, lps, msba, lipid transport
• 由来する生物種: Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 138535.67

構造登録者

Ho, H.,Koth, C.M.,Payandeh, J. (登録日: 2017-11-24, 公開日: 2018-05-02, 最終更新日: 2024-03-13)

主引用文献

Ho, H.,Miu, A.,Alexander, M.K.,Garcia, N.K.,Oh, A.,Zilberleyb, I.,Reichelt, M.,Austin, C.D.,Tam, C.,Shriver, S.,Hu, H.,Labadie, S.S.,Liang, J.,Wang, L.,Wang, J.,Lu, Y.,Purkey, H.E.,Quinn, J.,Franke, Y.,Clark, K.,Beresini, M.H.,Tan, M.W.,Sellers, B.D.,Maurer, T.,Koehler, M.F.T.,Wecksler, A.T.,Kiefer, J.R.,Verma, V.,Xu, Y.,Nishiyama, M.,Payandeh, J.,Koth, C.M.
Structural basis for dual-mode inhibition of the ABC transporter MsbA.
Nature, 557:196-201, 2018

PubMed Abstract: 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 Å 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.

PubMed: 29720648
DOI: 10.1038/s41586-018-0083-5

実験手法

X-RAY DIFFRACTION (2.92 Å)