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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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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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.</description><identifier>ISSN: 1522-1059</identifier><identifier>ISSN: 1550-7416</identifier><identifier>EISSN: 1522-1059</identifier><identifier>EISSN: 1550-7416</identifier><identifier>DOI: 10.1208/ps010202</identifier><identifier>PMID: 11741199</identifier><language>eng</language><publisher>United States: Springer-Verlag</publisher><subject>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</subject><ispartof>AAPS PharmSci, 1999-01, Vol.1 (2), p.E2-26</ispartof><rights>American Association of Pharmaceutical Scientists 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-be48af152c8d242afb4a9fe83d6a81d6e77f1d52d54c87b85c832743b5bd77343</citedby><cites>FETCH-LOGICAL-c538t-be48af152c8d242afb4a9fe83d6a81d6e77f1d52d54c87b85c832743b5bd77343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761117/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761117/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,729,782,786,887,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11741199$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Felder, C B</creatorcontrib><creatorcontrib>Graul, R C</creatorcontrib><creatorcontrib>Lee, A Y</creatorcontrib><creatorcontrib>Merkle, H P</creatorcontrib><creatorcontrib>Sadee, W</creatorcontrib><title>The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors</title><title>AAPS PharmSci</title><addtitle>AAPS PharmSci</addtitle><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.</description><subject>Animals</subject><subject>Artificial Gene Fusion</subject><subject>Bacterial Proteins - chemistry</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Carrier Proteins - chemistry</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Crystallography, X-Ray</subject><subject>Databases, Factual</subject><subject>Escherichia coli Proteins</subject><subject>Evolution, Molecular</subject><subject>Gram-Negative Bacteria - chemistry</subject><subject>Gram-Negative Bacteria - metabolism</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Lac Repressors</subject><subject>Ligands</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Models, Molecular</subject><subject>Peptides - chemistry</subject><subject>Protein Conformation</subject><subject>Receptors, Drug - chemistry</subject><subject>Receptors, Drug - genetics</subject><subject>Receptors, Drug - metabolism</subject><subject>Receptors, Glutamate - chemistry</subject><subject>Receptors, Glutamate - metabolism</subject><subject>Repressor Proteins - chemistry</subject><issn>1522-1059</issn><issn>1550-7416</issn><issn>1522-1059</issn><issn>1550-7416</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVtLBSEUhSWK7tAvCJ-ql1Pq6Oj0EER0g6CX6lUc3XMyZsZJZ4L-fR463V4CYevaH4uFC6E9So4pI-pkSIQSRtgK2qSCsRklolr9dd9AWym9EMJ4Jeg62qBUckqrahOFh2fAT9BPCTft-xjNgEODB4h-aE3qvMW1753v53iIYQTfp1Ns-nysh378EnEX3NRCfkJayAtlasfsAdjFaY4jWBjGENMOWmtMm2B3ObfR49Xlw8XN7O7--vbi_G5mRaHGWQ1cmSbnt8oxzkxTc1M1oApXGkVdCVI21AnmBLdK1kpYVTDJi1rUTsqCF9vo7NN3mOoOnM2pomn1EH1n4rsOxuu_m94_63l400yWNH9PNjhcGsTwOkEadeeThbY1PYQpaclFWdFSVJk8-JcsK8GoKhbg0SdoY0gpQvMdhxK96FF_9ZjR_d_xf8BlccUHHG2bYA</recordid><startdate>19990101</startdate><enddate>19990101</enddate><creator>Felder, C B</creator><creator>Graul, R C</creator><creator>Lee, A Y</creator><creator>Merkle, H P</creator><creator>Sadee, W</creator><general>Springer-Verlag</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QL</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>19990101</creationdate><title>The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors</title><author>Felder, C B ; Graul, R C ; Lee, A Y ; Merkle, H P ; Sadee, W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-be48af152c8d242afb4a9fe83d6a81d6e77f1d52d54c87b85c832743b5bd77343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Artificial Gene Fusion</topic><topic>Bacterial Proteins - chemistry</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Carrier Proteins - chemistry</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Crystallography, X-Ray</topic><topic>Databases, Factual</topic><topic>Escherichia coli Proteins</topic><topic>Evolution, Molecular</topic><topic>Gram-Negative Bacteria - chemistry</topic><topic>Gram-Negative Bacteria - metabolism</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Lac Repressors</topic><topic>Ligands</topic><topic>Membrane Transport Proteins - genetics</topic><topic>Models, Molecular</topic><topic>Peptides - chemistry</topic><topic>Protein Conformation</topic><topic>Receptors, Drug - chemistry</topic><topic>Receptors, Drug - genetics</topic><topic>Receptors, Drug - metabolism</topic><topic>Receptors, Glutamate - chemistry</topic><topic>Receptors, Glutamate - metabolism</topic><topic>Repressor Proteins - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Felder, C B</creatorcontrib><creatorcontrib>Graul, R C</creatorcontrib><creatorcontrib>Lee, A Y</creatorcontrib><creatorcontrib>Merkle, H P</creatorcontrib><creatorcontrib>Sadee, W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>AAPS PharmSci</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Felder, C B</au><au>Graul, R C</au><au>Lee, A Y</au><au>Merkle, H P</au><au>Sadee, W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Venus flytrap of periplasmic binding proteins: an ancient protein module present in multiple drug receptors</atitle><jtitle>AAPS PharmSci</jtitle><addtitle>AAPS PharmSci</addtitle><date>1999-01-01</date><risdate>1999</risdate><volume>1</volume><issue>2</issue><spage>E2</spage><epage>26</epage><pages>E2-26</pages><issn>1522-1059</issn><issn>1550-7416</issn><eissn>1522-1059</eissn><eissn>1550-7416</eissn><abstract>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.</abstract><cop>United States</cop><pub>Springer-Verlag</pub><pmid>11741199</pmid><doi>10.1208/ps010202</doi><tpages>20</tpages><oa>free_for_read</oa></addata></record> |
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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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