2QW1

Glucose/galactose binding protein bound to 3-O-methyl D-glucose

Summary for 2QW1

• Entry DOI: 10.2210/pdb2qw1/pdb
• Related: 2FVY 2FW0 2GBP
• Descriptor: D-galactose-binding periplasmic protein, 3-O-methyl-beta-D-glucopyranose, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: periplasmic binding protein, antagonist, chemotaxis, transport, ggbp, 3-o-methyl glucose, sugar transport, transport protein
• Biological source: Escherichia coli
• Cellular location: Periplasm: P0AEE5
• Total number of polymer chains: 1
• Total formula weight: 33687.87

Authors

Borrok, M.J.,Kiessling, L.L.,Forest, K.T. (deposition date: 2007-08-09, release date: 2008-08-05, Last modification date: 2023-08-30)

Primary citation

Borrok, M.J.,Zhu, Y.,Forest, K.T.,Kiessling, L.L.
Structure-based design of a periplasmic binding protein antagonist that prevents domain closure.
Acs Chem.Biol., 4:447-456, 2009

PubMed 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.

PubMed: 19348466
DOI: 10.1021/cb900021q

Experimental method

X-RAY DIFFRACTION (1.7 Å)