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PDBsum entry 2qw1
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Transport protein
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PDB id
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2qw1
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References listed in PDB file
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Key reference
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Title
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Structure-Based design of a periplasmic binding protein antagonist that prevents domain closure.
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Authors
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M.J.Borrok,
Y.Zhu,
K.T.Forest,
L.L.Kiessling.
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Ref.
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Acs Chem Biol, 2009,
4,
447-456.
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PubMed id
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Abstract
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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.
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