PDBsum entry 2qw1

Transport protein

PDB id: 2qw1

Contents

Protein chain

305 a.a. *

Ligands

3MG

Metals

_NA ×2

_CA

Waters ×352

* Residue conservation analysis

PDB id:

2qw1

Name:

Transport protein

Title:

Glucose/galactose binding protein bound to 3-o-methyl d-glucose

Structure:

D-galactose-binding periplasmic protein. Chain: a. Synonym: gbp, d-galactose/ d-glucose-binding protein, ggbp. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Strain: k12. Gene: mglb. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.70Å R-factor: 0.182 R-free: 0.204

Authors:

M.J.Borrok,L.L.Kiessling,K.T.Forest

Key ref:

M.J.Borrok et al. (2009). Structure-based design of a periplasmic binding protein antagonist that prevents domain closure. Acs Chem Biol, 4, 447-456. PubMed id: 19348466

Date:

09-Aug-07 Release date: 05-Aug-08

Protein chain

P0AEE5  (DGAL_ECOLI) -  D-galactose/methyl-galactoside binding periplasmic protein MglB from Escherichia coli (strain K12)

Seq: 332 a.a.

Struc: 305 a.a.

Enzyme reactions

• Enzyme class: E.C.?

Acs Chem Biol 4:447-456 (2009)

PubMed id: 19348466

Structure-based design of a periplasmic binding protein antagonist that prevents domain closure.

M.J.Borrok, Y.Zhu, K.T.Forest, L.L.Kiessling.

ABSTRACT

Many receptors undergo ligand-induced conformational changes to initiate signal transduction. Periplasmic binding proteins (PBPs) are bacterial receptors that exhibit dramatic conformational changes upon ligand binding. These proteins mediate a wide variety of fundamental processes including transport, chemotaxis, and quorum sensing. Despite the importance of these receptors, no PBP antagonists have been identified and characterized. In this study, we identify 3-O-methyl-d-glucose as an antagonist of glucose/galactose-binding protein and demonstrate that it inhibits glucose chemotaxis in E. coli. Using small-angle X-ray scattering and X-ray crystallography, we show that this antagonist acts as a wedge. It prevents the large-scale domain closure that gives rise to the active signaling state. Guided by these results and the structures of open and closed glucose/galactose-binding protein, we designed and synthesized an antagonist composed of two linked glucose residues. These findings provide a blueprint for the design of new bacterial PBP inhibitors. Given the key role of PBPs in microbial physiology, we anticipate that PBP antagonists will have widespread uses as probes and antimicrobial agents.