PDBsum entry 6bpp

Lipid transport

PDB id: 6bpp

Contents

Protein chains

576 a.a.

Ligands

PA1-GCS-KDO-GMH-GMH-GLC-GLC-GLC-GMH-KDO

E1M ×2

FTT ×4

DAO

3PE ×7

PO4 ×2

MYR

PDB id:

6bpp

Name:

Lipid transport

Title:

E. Coli msba in complex with lps and inhibitor g092

Structure:

Lipid a export atp-binding/permease protein msba. Chain: a, b. Engineered: yes

Source:

Escherichia coli o6:h1 (strain cft073 / atcc 700928 / upec). Organism_taxid: 199310. Strain: cft073 / atcc 700928 / upec. Gene: msba, c1054. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.92Å R-factor: 0.259 R-free: 0.278

Authors:

H.Ho,C.M.Koth,J.Payandeh

Key ref:

H.Ho et al. (2018). Structural basis for dual-mode inhibition of the ABC transporter MsbA. Nature, 557, 196-201. PubMed id: 29720648 DOI: 10.1038/s41586-018-0083-5

Date:

24-Nov-17 Release date: 02-May-18

Protein chains

Q8FJB1  (MSBA_ECOL6) -  ATP-dependent lipid A-core flippase from Escherichia coli O6:H1 (strain CFT073 / ATCC 700928 / UPEC)

Seq: 582 a.a.

Struc: 576 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.7.5.2.6 - ABC-type lipid A-core oligosaccharide transporter.
• Reaction: ATP + H2O + lipid A-core oligosaccharideSide 1 = ADP + phosphate + lipid A-core oligosaccharideSide 2

ATP + H2O + lipid A-core oligosaccharideSide 1 = ADP + phosphate (Bound ligand (Het Group name = 3PE) matches with 50.00% similarity) + lipid A-core oligosaccharideSide 2

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/s41586-018-0083-5

Nature 557:196-201 (2018)

PubMed id: 29720648

Structural basis for dual-mode inhibition of the ABC transporter MsbA.

H.Ho, A.Miu, M.K.Alexander, N.K.Garcia, A.Oh, I.Zilberleyb, M.Reichelt, C.D.Austin, C.Tam, S.Shriver, H.Hu, S.S.Labadie, J.Liang, L.Wang, J.Wang, Y.Lu, H.E.Purkey, J.Quinn, Y.Franke, K.Clark, M.H.Beresini, M.W.Tan, B.D.Sellers, T.Maurer, M.F.T.Koehler, A.T.Wecksler, J.R.Kiefer, V.Verma, Y.Xu, M.Nishiyama, J.Payandeh, C.M.Koth.

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.