The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors

Located between the inner and outer membranes of Gram-negative bacteria, periplasmic binding proteins (PBPs) scavenge or sense diverse nutrients in the environment by coupling to transporters or chemotaxis receptors in the inner membrane. Their three-dimensional structures have been deduced in atomi...

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Veröffentlicht in:AAPS PharmSci 1999-01, Vol.1 (2), p.E2-26
Hauptverfasser: Felder, C B, Graul, R C, Lee, A Y, Merkle, H P, Sadee, W
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creator Felder, C B
Graul, R C
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Merkle, H P
Sadee, W
description Located between the inner and outer membranes of Gram-negative bacteria, periplasmic binding proteins (PBPs) scavenge or sense diverse nutrients in the environment by coupling to transporters or chemotaxis receptors in the inner membrane. Their three-dimensional structures have been deduced in atomic detail with the use of X-ray crystallography, both in the free and liganded state. PBPs consist of two large lobes that close around the bound ligand, resembling a Venus flytrap. This architecture is reiterated in transcriptional regulators, such as the lac repressors. In the process of evolution, genes encoding the PBPs have fused with genes for integral membrane proteins. Thus, diverse mammalian receptors contain extracellular ligand binding domains that are homologous to the PBPs; these include glutamate/glycine-gated ion channels such as the NMDA receptor, G protein-coupled receptors, including metabotropic glutamate, GABA-B, calcium sensing, and pheromone receptors, and atrial natriuretic peptide-guanylate cyclase receptors. Many of these receptors are promising drug targets. On the basis of homology to PBPs and a recently resolved crystal structure of the extracellular binding domain of a glutamate receptor ion channel, it is possible to construct three-dimensional models of their ligand binding domains. Together with the extensive information available on the mechanism of ligand binding to PBPs, such models can serve as a guide in drug discovery.
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identifier ISSN: 1522-1059
ispartof AAPS PharmSci, 1999-01, Vol.1 (2), p.E2-26
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1522-1059
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source MEDLINE; PubMed Central
subjects Animals
Artificial Gene Fusion
Bacterial Proteins - chemistry
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Carrier Proteins - chemistry
Carrier Proteins - genetics
Carrier Proteins - metabolism
Crystallography, X-Ray
Databases, Factual
Escherichia coli Proteins
Evolution, Molecular
Gram-Negative Bacteria - chemistry
Gram-Negative Bacteria - metabolism
GTP-Binding Proteins - metabolism
Lac Repressors
Ligands
Membrane Transport Proteins - genetics
Models, Molecular
Peptides - chemistry
Protein Conformation
Receptors, Drug - chemistry
Receptors, Drug - genetics
Receptors, Drug - metabolism
Receptors, Glutamate - chemistry
Receptors, Glutamate - metabolism
Repressor Proteins - chemistry
title The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors
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