PDBsum entry 6b8b

Lipid transport/activator

PDB id: 6b8b

Contents

Protein chain

233 a.a.

Ligands

CZJ

ADP

Metals

_MG

Waters ×105

PDB id:

6b8b

Name:

Lipid transport/activator

Title:

E. Coli lptb in complex with adp and a novobiocin derivative

Structure:

Lipopolysaccharide export system atp-binding protein lptb. Chain: a. Engineered: yes

Source:

Escherichia coli (strain k12). Organism_taxid: 83333. Strain: k12. Gene: lptb, yhbg, b3201, jw3168. Expressed in: escherichia coli krx. Expression_system_taxid: 1452720

Resolution:

1.95Å R-factor: 0.182 R-free: 0.224

Authors:

M.D.Mandler,T.W.Owens,M.B.Lazarus,J.M.May,D.K.Kahne

Key ref:

J.M.May et al. (2017). The Antibiotic Novobiocin Binds and Activates the ATPase That Powers Lipopolysaccharide Transport. J Am Chem Soc, 139, 17221-17224. PubMed id: 29135241

Date:

06-Oct-17 Release date: 06-Dec-17

Protein chain

P0A9V1  (LPTB_ECOLI) -  Lipopolysaccharide export system ATP-binding protein LptB from Escherichia coli (strain K12)

Seq: 241 a.a.

Struc: 233 a.a.

Enzyme reactions

• Enzyme class: E.C.7.5.2.- - ?????

J Am Chem Soc 139:17221-17224 (2017)

PubMed id: 29135241

The Antibiotic Novobiocin Binds and Activates the ATPase That Powers Lipopolysaccharide Transport.

J.M.May, T.W.Owens, M.D.Mandler, B.W.Simpson, M.B.Lazarus, D.J.Sherman, R.M.Davis, S.Okuda, W.Massefski, N.Ruiz, D.Kahne.

ABSTRACT

Novobiocin is an orally active antibiotic that inhibits DNA gyrase by binding the ATP-binding site in the ATPase subunit. Although effective against Gram-positive pathogens, novobiocin has limited activity against Gram-negative organisms due to the presence of the lipopolysaccharide-containing outer membrane, which acts as a permeability barrier. Using a novobiocin-sensitive Escherichia coli strain with a leaky outer membrane, we identified a mutant with increased resistance to novobiocin. Unexpectedly, the mutation that increases novobiocin resistance was not found to alter gyrase, but the ATPase that powers lipopolysaccharide (LPS) transport. Co-crystal structures, biochemical, and genetic evidence show novobiocin directly binds this ATPase. Novobiocin does not bind the ATP binding site but rather the interface between the ATPase subunits and the transmembrane subunits of the LPS transporter. This interaction increases the activity of the LPS transporter, which in turn alters the permeability of the outer membrane. We propose that novobiocin will be a useful tool for understanding how ATP hydrolysis is coupled to LPS transport.