Crystal structure of human PNP complexed with guanine
Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2003-12, Vol.312 (3), p.767-772 |
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| container_title | Biochemical and biophysical research communications |
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| creator | de Azevedo, Walter Filgueira Canduri, Fernanda dos Santos, Denis Marangoni Pereira, José Henrique Bertacine Dias, Márcio Vinicius Silva, Rafael Guimarães Mendes, Maria Anita Basso, Luiz Augusto Palma, Mário Sérgio Santos, Diógenes Santiago |
| description | Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the
N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently, the 3-D structure of human PNP has been refined to 2.3
Å resolution, which allowed a redefinition of the residues involved in the substrate-binding sites and provided a more reliable model for structure-based design of inhibitors. This work reports crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7
Å resolution using synchrotron radiation. Analysis of the structural differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design. |
| doi_str_mv | 10.1016/j.bbrc.2003.10.190 |
| format | Article |
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N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently, the 3-D structure of human PNP has been refined to 2.3
Å resolution, which allowed a redefinition of the residues involved in the substrate-binding sites and provided a more reliable model for structure-based design of inhibitors. This work reports crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7
Å resolution using synchrotron radiation. Analysis of the structural differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2003.10.190</identifier><identifier>PMID: 14680831</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Binding Sites ; Computer Simulation ; Crystallization - methods ; Crystallography - methods ; Drug design ; Enzyme Activation ; Guanine - chemistry ; Humans ; Macromolecular Substances ; Models, Molecular ; Phosphates - chemistry ; PNP ; Protein Binding ; Protein Conformation ; Purine-Nucleoside Phosphorylase - chemistry ; Solutions ; Structure ; Substrate Specificity ; Synchrotron radiation ; Teprotide ; Water - chemistry</subject><ispartof>Biochemical and biophysical research communications, 2003-12, Vol.312 (3), p.767-772</ispartof><rights>2003 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-99e6f17f86c3391aba24226220998bb6ff345647e2e72ca9e290bdb35fb2b1e53</citedby><cites>FETCH-LOGICAL-c385t-99e6f17f86c3391aba24226220998bb6ff345647e2e72ca9e290bdb35fb2b1e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2003.10.190$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14680831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Azevedo, Walter Filgueira</creatorcontrib><creatorcontrib>Canduri, Fernanda</creatorcontrib><creatorcontrib>dos Santos, Denis Marangoni</creatorcontrib><creatorcontrib>Pereira, José Henrique</creatorcontrib><creatorcontrib>Bertacine Dias, Márcio Vinicius</creatorcontrib><creatorcontrib>Silva, Rafael Guimarães</creatorcontrib><creatorcontrib>Mendes, Maria Anita</creatorcontrib><creatorcontrib>Basso, Luiz Augusto</creatorcontrib><creatorcontrib>Palma, Mário Sérgio</creatorcontrib><creatorcontrib>Santos, Diógenes Santiago</creatorcontrib><title>Crystal structure of human PNP complexed with guanine</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the
N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently, the 3-D structure of human PNP has been refined to 2.3
Å resolution, which allowed a redefinition of the residues involved in the substrate-binding sites and provided a more reliable model for structure-based design of inhibitors. This work reports crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7
Å resolution using synchrotron radiation. Analysis of the structural differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.</description><subject>Binding Sites</subject><subject>Computer Simulation</subject><subject>Crystallization - methods</subject><subject>Crystallography - methods</subject><subject>Drug design</subject><subject>Enzyme Activation</subject><subject>Guanine - chemistry</subject><subject>Humans</subject><subject>Macromolecular Substances</subject><subject>Models, Molecular</subject><subject>Phosphates - chemistry</subject><subject>PNP</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Purine-Nucleoside Phosphorylase - chemistry</subject><subject>Solutions</subject><subject>Structure</subject><subject>Substrate Specificity</subject><subject>Synchrotron radiation</subject><subject>Teprotide</subject><subject>Water - chemistry</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDtPwzAUhS0EouXxBxhQJraEazsvSyyo4iVV0AEkNst2bqirPIqdAP33JLQSG0xHOjrnGz5CzihEFGh6uYq0diZiADwaOwF7ZEpBQMgoxPtkCgBpyAR9nZAj71cAlMapOCSTIXLIOZ2SZOY2vlNV4DvXm653GLRlsOxr1QSLx0Vg2npd4RcWwaftlsFbrxrb4Ak5KFXl8XSXx-Tl9uZ5dh_On-4eZtfz0PA86UIhMC1pVuap4VxQpRWLGUsZAyFyrdOy5HGSxhkyzJhRApkAXWielJppigk_Jhdb7tq17z36TtbWG6wq1WDbe5nRBOI44_8OqWA0T7KRyLZD41rvHZZy7Wyt3EZSkKNVuZKjVTla_ekEDKfzHb3XNRa_l53GYXC1HeAg48Oik95YbAwW1qHpZNHav_jfayeHHg</recordid><startdate>20031219</startdate><enddate>20031219</enddate><creator>de Azevedo, Walter Filgueira</creator><creator>Canduri, Fernanda</creator><creator>dos Santos, Denis Marangoni</creator><creator>Pereira, José Henrique</creator><creator>Bertacine Dias, Márcio Vinicius</creator><creator>Silva, Rafael Guimarães</creator><creator>Mendes, Maria Anita</creator><creator>Basso, Luiz Augusto</creator><creator>Palma, Mário Sérgio</creator><creator>Santos, Diógenes Santiago</creator><general>Elsevier Inc</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20031219</creationdate><title>Crystal structure of human PNP complexed with guanine</title><author>de Azevedo, Walter Filgueira ; Canduri, Fernanda ; dos Santos, Denis Marangoni ; Pereira, José Henrique ; Bertacine Dias, Márcio Vinicius ; Silva, Rafael Guimarães ; Mendes, Maria Anita ; Basso, Luiz Augusto ; Palma, Mário Sérgio ; Santos, Diógenes Santiago</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-99e6f17f86c3391aba24226220998bb6ff345647e2e72ca9e290bdb35fb2b1e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Binding Sites</topic><topic>Computer Simulation</topic><topic>Crystallization - methods</topic><topic>Crystallography - methods</topic><topic>Drug design</topic><topic>Enzyme Activation</topic><topic>Guanine - chemistry</topic><topic>Humans</topic><topic>Macromolecular Substances</topic><topic>Models, Molecular</topic><topic>Phosphates - chemistry</topic><topic>PNP</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Purine-Nucleoside Phosphorylase - chemistry</topic><topic>Solutions</topic><topic>Structure</topic><topic>Substrate Specificity</topic><topic>Synchrotron radiation</topic><topic>Teprotide</topic><topic>Water - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Azevedo, Walter Filgueira</creatorcontrib><creatorcontrib>Canduri, Fernanda</creatorcontrib><creatorcontrib>dos Santos, Denis Marangoni</creatorcontrib><creatorcontrib>Pereira, José Henrique</creatorcontrib><creatorcontrib>Bertacine Dias, Márcio Vinicius</creatorcontrib><creatorcontrib>Silva, Rafael Guimarães</creatorcontrib><creatorcontrib>Mendes, Maria Anita</creatorcontrib><creatorcontrib>Basso, Luiz Augusto</creatorcontrib><creatorcontrib>Palma, Mário Sérgio</creatorcontrib><creatorcontrib>Santos, Diógenes Santiago</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Azevedo, Walter Filgueira</au><au>Canduri, Fernanda</au><au>dos Santos, Denis Marangoni</au><au>Pereira, José Henrique</au><au>Bertacine Dias, Márcio Vinicius</au><au>Silva, Rafael Guimarães</au><au>Mendes, Maria Anita</au><au>Basso, Luiz Augusto</au><au>Palma, Mário Sérgio</au><au>Santos, Diógenes Santiago</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Crystal structure of human PNP complexed with guanine</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2003-12-19</date><risdate>2003</risdate><volume>312</volume><issue>3</issue><spage>767</spage><epage>772</epage><pages>767-772</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the
N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently, the 3-D structure of human PNP has been refined to 2.3
Å resolution, which allowed a redefinition of the residues involved in the substrate-binding sites and provided a more reliable model for structure-based design of inhibitors. This work reports crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7
Å resolution using synchrotron radiation. Analysis of the structural differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>14680831</pmid><doi>10.1016/j.bbrc.2003.10.190</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Binding Sites Computer Simulation Crystallization - methods Crystallography - methods Drug design Enzyme Activation Guanine - chemistry Humans Macromolecular Substances Models, Molecular Phosphates - chemistry PNP Protein Binding Protein Conformation Purine-Nucleoside Phosphorylase - chemistry Solutions Structure Substrate Specificity Synchrotron radiation Teprotide Water - chemistry |
| title | Crystal structure of human PNP complexed with guanine |
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