Structure of the subtilisin Carlsberg-OMTKY3 complex reveals two different ovomucoid conformations
One of the most studied protein proteinase inhibitors is the turkey ovomucoid third domain, OMTKY3. This inhibitor contains a reactive‐site loop (Lys13I–Arg21I) that binds in a nearly identical manner to all studied serine proteinases, regardless of their clan or specificity. The crystal structure o...
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| Veröffentlicht in: | Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2005-05, Vol.61 (5), p.580-588 |
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| container_title | Acta crystallographica. Section D, Biological crystallography. |
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| creator | Cherney, Maia M. Qasim, M. A. Maynes, Jason T. Laskowski Jr, Michael James, Michael N. G. |
| description | One of the most studied protein proteinase inhibitors is the turkey ovomucoid third domain, OMTKY3. This inhibitor contains a reactive‐site loop (Lys13I–Arg21I) that binds in a nearly identical manner to all studied serine proteinases, regardless of their clan or specificity. The crystal structure of OMTKY3 bound to subtilisin Carlsberg (CARL) has been determined. There are two complete copies of the complexes in the crystallographic asymmetric unit. Whereas the two enzyme molecules are virtually identical [0.16 Å root‐mean‐square difference (r.m.s.d.) for 274 Cα atoms], the two inhibitor molecules show dramatic differences between one another (r.m.s.d. = 2.4 Å for 50 Cα atoms). When compared with other proteinase‐bound OMTKY3 molecules, these inhibitors show even larger differences. This work facilitates a re‐evaluation of the importance of certain ovomucoid residues in proteinase binding and explains why additivity and sequence‐based binding‐prediction methods fail for the CARL–OMTKY3 complex. |
| doi_str_mv | 10.1107/S0907444905004889 |
| format | Article |
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A. ; Maynes, Jason T. ; Laskowski Jr, Michael ; James, Michael N. G.</creator><creatorcontrib>Cherney, Maia M. ; Qasim, M. A. ; Maynes, Jason T. ; Laskowski Jr, Michael ; James, Michael N. G.</creatorcontrib><description>One of the most studied protein proteinase inhibitors is the turkey ovomucoid third domain, OMTKY3. This inhibitor contains a reactive‐site loop (Lys13I–Arg21I) that binds in a nearly identical manner to all studied serine proteinases, regardless of their clan or specificity. The crystal structure of OMTKY3 bound to subtilisin Carlsberg (CARL) has been determined. There are two complete copies of the complexes in the crystallographic asymmetric unit. Whereas the two enzyme molecules are virtually identical [0.16 Å root‐mean‐square difference (r.m.s.d.) for 274 Cα atoms], the two inhibitor molecules show dramatic differences between one another (r.m.s.d. = 2.4 Å for 50 Cα atoms). When compared with other proteinase‐bound OMTKY3 molecules, these inhibitors show even larger differences. This work facilitates a re‐evaluation of the importance of certain ovomucoid residues in proteinase binding and explains why additivity and sequence‐based binding‐prediction methods fail for the CARL–OMTKY3 complex.</description><identifier>ISSN: 1399-0047</identifier><identifier>ISSN: 0907-4449</identifier><identifier>EISSN: 1399-0047</identifier><identifier>DOI: 10.1107/S0907444905004889</identifier><identifier>PMID: 15858268</identifier><language>eng</language><publisher>5 Abbey Square, Chester, Cheshire CH1 2HU, England: Munksgaard International Publishers</publisher><subject>Animals ; Cattle ; Chymotrypsin - chemistry ; Crystallography, X-Ray ; Data Interpretation, Statistical ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Humans ; Leukocyte Elastase - chemistry ; Models, Molecular ; Ovomucin - chemistry ; Protein Binding ; Protein Conformation ; protein proteinase inhibitors ; proteinases ; Structure-Activity Relationship ; Subtilisins - antagonists & inhibitors ; Subtilisins - chemistry ; Turkeys</subject><ispartof>Acta crystallographica. 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A.</creatorcontrib><creatorcontrib>Maynes, Jason T.</creatorcontrib><creatorcontrib>Laskowski Jr, Michael</creatorcontrib><creatorcontrib>James, Michael N. G.</creatorcontrib><title>Structure of the subtilisin Carlsberg-OMTKY3 complex reveals two different ovomucoid conformations</title><title>Acta crystallographica. Section D, Biological crystallography.</title><addtitle>Acta Cryst. D</addtitle><description>One of the most studied protein proteinase inhibitors is the turkey ovomucoid third domain, OMTKY3. This inhibitor contains a reactive‐site loop (Lys13I–Arg21I) that binds in a nearly identical manner to all studied serine proteinases, regardless of their clan or specificity. The crystal structure of OMTKY3 bound to subtilisin Carlsberg (CARL) has been determined. There are two complete copies of the complexes in the crystallographic asymmetric unit. Whereas the two enzyme molecules are virtually identical [0.16 Å root‐mean‐square difference (r.m.s.d.) for 274 Cα atoms], the two inhibitor molecules show dramatic differences between one another (r.m.s.d. = 2.4 Å for 50 Cα atoms). When compared with other proteinase‐bound OMTKY3 molecules, these inhibitors show even larger differences. This work facilitates a re‐evaluation of the importance of certain ovomucoid residues in proteinase binding and explains why additivity and sequence‐based binding‐prediction methods fail for the CARL–OMTKY3 complex.</description><subject>Animals</subject><subject>Cattle</subject><subject>Chymotrypsin - chemistry</subject><subject>Crystallography, X-Ray</subject><subject>Data Interpretation, Statistical</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Leukocyte Elastase - chemistry</subject><subject>Models, Molecular</subject><subject>Ovomucin - chemistry</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>protein proteinase inhibitors</subject><subject>proteinases</subject><subject>Structure-Activity Relationship</subject><subject>Subtilisins - antagonists & inhibitors</subject><subject>Subtilisins - chemistry</subject><subject>Turkeys</subject><issn>1399-0047</issn><issn>0907-4449</issn><issn>1399-0047</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PFTEUhidGIoj-ADdmVu5G2-n0a3kdEAggCzAEN03bOdXqzPTadvj499bcGzFh4aqnyfO8OeetqjcYvccY8Q-XSCLedZ1EFKFOCPms2sNEyqb8-PN_5t3qZUo_EEJtS_iLahdTQUXLxF5lLnNcbF4i1MHV-TvUaTHZjz75ue51HJOB-K25OL86vSG1DdN6hPs6wi3oMdX5LtSDdw4izLkOt2FabPBD4WYX4qSzD3N6Ve24AsPr7btfffl0eNUfN2cXRyf96qyxRDDaDI47jIZyjmuZAQbSShCICmYw5xI7yrXRRHR2kIMzhmptGWGmw9aaAVqyX73b5K5j-LVAymryycI46hnCkhQrKRJ1pIB4A9oYUorg1Dr6SccHhZH6U6x6Umxx3m7DFzPB8GhsmyyA2AB3foSH_yeq1c3B4YoiQovabFSfMtz_VXX8WXYmnKrrz0fqa8_OZf_xWnXkN38alL0</recordid><startdate>200505</startdate><enddate>200505</enddate><creator>Cherney, Maia M.</creator><creator>Qasim, M. 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G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3865-df7f10d444f26be6e9c9e80586b17791f57aba384cd9dfbb5aac636b41ccbde23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Cattle</topic><topic>Chymotrypsin - chemistry</topic><topic>Crystallography, X-Ray</topic><topic>Data Interpretation, Statistical</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Humans</topic><topic>Leukocyte Elastase - chemistry</topic><topic>Models, Molecular</topic><topic>Ovomucin - chemistry</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>protein proteinase inhibitors</topic><topic>proteinases</topic><topic>Structure-Activity Relationship</topic><topic>Subtilisins - antagonists & inhibitors</topic><topic>Subtilisins - chemistry</topic><topic>Turkeys</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cherney, Maia M.</creatorcontrib><creatorcontrib>Qasim, M. A.</creatorcontrib><creatorcontrib>Maynes, Jason T.</creatorcontrib><creatorcontrib>Laskowski Jr, Michael</creatorcontrib><creatorcontrib>James, Michael N. G.</creatorcontrib><collection>Istex</collection><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>Acta crystallographica. Section D, Biological crystallography.</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cherney, Maia M.</au><au>Qasim, M. A.</au><au>Maynes, Jason T.</au><au>Laskowski Jr, Michael</au><au>James, Michael N. G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure of the subtilisin Carlsberg-OMTKY3 complex reveals two different ovomucoid conformations</atitle><jtitle>Acta crystallographica. Section D, Biological crystallography.</jtitle><addtitle>Acta Cryst. D</addtitle><date>2005-05</date><risdate>2005</risdate><volume>61</volume><issue>5</issue><spage>580</spage><epage>588</epage><pages>580-588</pages><issn>1399-0047</issn><issn>0907-4449</issn><eissn>1399-0047</eissn><abstract>One of the most studied protein proteinase inhibitors is the turkey ovomucoid third domain, OMTKY3. This inhibitor contains a reactive‐site loop (Lys13I–Arg21I) that binds in a nearly identical manner to all studied serine proteinases, regardless of their clan or specificity. The crystal structure of OMTKY3 bound to subtilisin Carlsberg (CARL) has been determined. There are two complete copies of the complexes in the crystallographic asymmetric unit. Whereas the two enzyme molecules are virtually identical [0.16 Å root‐mean‐square difference (r.m.s.d.) for 274 Cα atoms], the two inhibitor molecules show dramatic differences between one another (r.m.s.d. = 2.4 Å for 50 Cα atoms). When compared with other proteinase‐bound OMTKY3 molecules, these inhibitors show even larger differences. This work facilitates a re‐evaluation of the importance of certain ovomucoid residues in proteinase binding and explains why additivity and sequence‐based binding‐prediction methods fail for the CARL–OMTKY3 complex.</abstract><cop>5 Abbey Square, Chester, Cheshire CH1 2HU, England</cop><pub>Munksgaard International Publishers</pub><pmid>15858268</pmid><doi>10.1107/S0907444905004889</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Cattle Chymotrypsin - chemistry Crystallography, X-Ray Data Interpretation, Statistical Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Humans Leukocyte Elastase - chemistry Models, Molecular Ovomucin - chemistry Protein Binding Protein Conformation protein proteinase inhibitors proteinases Structure-Activity Relationship Subtilisins - antagonists & inhibitors Subtilisins - chemistry Turkeys |
| title | Structure of the subtilisin Carlsberg-OMTKY3 complex reveals two different ovomucoid conformations |
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