Concerted Structural Changes in the Peptidase and the Propeller Domains of Prolyl Oligopeptidase are Required for Substrate Binding
Prolyl oligopeptidase contains a peptidase domain and its catalytic triad is covered by the central tunnel of a seven-bladed β-propeller. This domain makes the enzyme an oligopeptidase by excluding large structured peptides from the active site. The apparently rigid crystal structure does not explai...
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| Veröffentlicht in: | Journal of molecular biology 2004-07, Vol.340 (3), p.627-637 |
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| container_title | Journal of molecular biology |
| container_volume | 340 |
| creator | Szeltner, Zoltán Rea, Dean Juhász, Tünde Renner, Veronika Fülöp, Vilmos Polgár, László |
| description | Prolyl oligopeptidase contains a peptidase domain and its catalytic triad is covered by the central tunnel of a seven-bladed β-propeller. This domain makes the enzyme an oligopeptidase by excluding large structured peptides from the active site. The apparently rigid crystal structure does not explain how the substrate can approach the catalytic groups. Two possibilities of substrate access were investigated: either blades 1 and 7 of the propeller domain move apart, or the peptidase and/or propeller domains move to create an entry site at the domain interface. Engineering disulfide bridges to the expected oscillating structures prevented such movements, which destroyed the catalytic activity and precluded substrate binding. This indicated that concerted movements of the propeller and the peptidase domains are essential for the enzyme action. |
| doi_str_mv | 10.1016/j.jmb.2004.05.011 |
| format | Article |
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This domain makes the enzyme an oligopeptidase by excluding large structured peptides from the active site. The apparently rigid crystal structure does not explain how the substrate can approach the catalytic groups. Two possibilities of substrate access were investigated: either blades 1 and 7 of the propeller domain move apart, or the peptidase and/or propeller domains move to create an entry site at the domain interface. Engineering disulfide bridges to the expected oscillating structures prevented such movements, which destroyed the catalytic activity and precluded substrate binding. 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This domain makes the enzyme an oligopeptidase by excluding large structured peptides from the active site. The apparently rigid crystal structure does not explain how the substrate can approach the catalytic groups. Two possibilities of substrate access were investigated: either blades 1 and 7 of the propeller domain move apart, or the peptidase and/or propeller domains move to create an entry site at the domain interface. Engineering disulfide bridges to the expected oscillating structures prevented such movements, which destroyed the catalytic activity and precluded substrate binding. This indicated that concerted movements of the propeller and the peptidase domains are essential for the enzyme action.</description><subject>Catalysis</subject><subject>disulfide bond formation</subject><subject>Disulfides - chemistry</subject><subject>Models, Molecular</subject><subject>Peptide Hydrolases - chemistry</subject><subject>Peptide Hydrolases - metabolism</subject><subject>Protein Conformation</subject><subject>protein stability</subject><subject>Serine Endopeptidases - chemistry</subject><subject>Serine Endopeptidases - metabolism</subject><subject>site-specific mutagenesis</subject><subject>substrate binding</subject><subject>Substrate Specificity</subject><issn>0022-2836</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFv1DAQhS1ERbeFH8AF-cQtweM4TlacYKFQqVIRhbPl2OOtV0m8tR2knvvH8WpXcOtpNOP33ng-Qt4Cq4GB_LCrd9NQc8ZEzdqaAbwgK2D9uupl078kK8Y4r3jfyHNykdKOMdY2on9FzqHlwJp2vSJPmzAbjBktvctxMXmJeqSbez1vMVE_03yP9Afus7c6IdWzPU5i2OM4YqRfwqT9nGhwh-H4ONLb0W_L6z9LRPoTHxYfyw4XIr1bhpSjzkg_-9n6efuanDk9Jnxzqpfk99XXX5vv1c3tt-vNp5vKCGhzha58XvQMht6uBTcSNDLZSSlZV1p0nTC9kwPIlnPLQbhBarCdc7YTPbbNJXl_zN3H8LBgymryyZQz9IxhSaokCeASihCOQhNDShGd2kc_6fiogKkDebVThbw6kFesVYV88bw7hS_DhPa_44S6CD4eBVhO_OMxqmQ8Fvi2kDFZ2eCfif8LgsyVTw</recordid><startdate>20040709</startdate><enddate>20040709</enddate><creator>Szeltner, Zoltán</creator><creator>Rea, Dean</creator><creator>Juhász, Tünde</creator><creator>Renner, Veronika</creator><creator>Fülöp, Vilmos</creator><creator>Polgár, László</creator><general>Elsevier Ltd</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></search><sort><creationdate>20040709</creationdate><title>Concerted Structural Changes in the Peptidase and the Propeller Domains of Prolyl Oligopeptidase are Required for Substrate Binding</title><author>Szeltner, Zoltán ; Rea, Dean ; Juhász, Tünde ; Renner, Veronika ; Fülöp, Vilmos ; Polgár, László</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-ef3484801b8d942c61ae0676660742cef74c8f6b16522d214fb6a1d7ffd748e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Catalysis</topic><topic>disulfide bond formation</topic><topic>Disulfides - chemistry</topic><topic>Models, Molecular</topic><topic>Peptide Hydrolases - chemistry</topic><topic>Peptide Hydrolases - metabolism</topic><topic>Protein Conformation</topic><topic>protein stability</topic><topic>Serine Endopeptidases - chemistry</topic><topic>Serine Endopeptidases - metabolism</topic><topic>site-specific mutagenesis</topic><topic>substrate binding</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Szeltner, Zoltán</creatorcontrib><creatorcontrib>Rea, Dean</creatorcontrib><creatorcontrib>Juhász, Tünde</creatorcontrib><creatorcontrib>Renner, Veronika</creatorcontrib><creatorcontrib>Fülöp, Vilmos</creatorcontrib><creatorcontrib>Polgár, László</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><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Szeltner, Zoltán</au><au>Rea, Dean</au><au>Juhász, Tünde</au><au>Renner, Veronika</au><au>Fülöp, Vilmos</au><au>Polgár, László</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Concerted Structural Changes in the Peptidase and the Propeller Domains of Prolyl Oligopeptidase are Required for Substrate Binding</atitle><jtitle>Journal of molecular biology</jtitle><addtitle>J Mol Biol</addtitle><date>2004-07-09</date><risdate>2004</risdate><volume>340</volume><issue>3</issue><spage>627</spage><epage>637</epage><pages>627-637</pages><issn>0022-2836</issn><eissn>1089-8638</eissn><abstract>Prolyl oligopeptidase contains a peptidase domain and its catalytic triad is covered by the central tunnel of a seven-bladed β-propeller. This domain makes the enzyme an oligopeptidase by excluding large structured peptides from the active site. The apparently rigid crystal structure does not explain how the substrate can approach the catalytic groups. Two possibilities of substrate access were investigated: either blades 1 and 7 of the propeller domain move apart, or the peptidase and/or propeller domains move to create an entry site at the domain interface. Engineering disulfide bridges to the expected oscillating structures prevented such movements, which destroyed the catalytic activity and precluded substrate binding. This indicated that concerted movements of the propeller and the peptidase domains are essential for the enzyme action.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>15210359</pmid><doi>10.1016/j.jmb.2004.05.011</doi><tpages>11</tpages></addata></record> |
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| ispartof | Journal of molecular biology, 2004-07, Vol.340 (3), p.627-637 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Catalysis disulfide bond formation Disulfides - chemistry Models, Molecular Peptide Hydrolases - chemistry Peptide Hydrolases - metabolism Protein Conformation protein stability Serine Endopeptidases - chemistry Serine Endopeptidases - metabolism site-specific mutagenesis substrate binding Substrate Specificity |
| title | Concerted Structural Changes in the Peptidase and the Propeller Domains of Prolyl Oligopeptidase are Required for Substrate Binding |
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