Triad of polar residues implicated in pH specificity of acidic mammalian chitinase
Acidic mammalian chitinase (AMCase) is a mammalian chitinase that has been implicated in allergic asthma. One of only two active mammalian chinases, AMCase, is distinguished from other chitinases by several unique features. Here, we present the novel structure of the AMCase catalytic domain, both in...
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| Veröffentlicht in: | Protein science 2009-03, Vol.18 (3), p.569-578 |
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| creator | Olland, Andrea M. Strand, James Presman, Eleonora Czerwinski, Robert Joseph‐McCarthy, Diane Krykbaev, Rustem Schlingmann, Gerhard Chopra, Rajiv Lin, Laura Fleming, Margaret Kriz, Ron Stahl, Mark Somers, William Fitz, Lori Mosyak, Lidia |
| description | Acidic mammalian chitinase (AMCase) is a mammalian chitinase that has been implicated in allergic asthma. One of only two active mammalian chinases, AMCase, is distinguished from other chitinases by several unique features. Here, we present the novel structure of the AMCase catalytic domain, both in the apo form and in complex with the inhibitor methylallosamidin, determined to high resolution by X‐ray crystallography. These results provide a structural basis for understanding some of the unique characteristics of this enzyme, including the low pH optimum and the preference for the β‐anomer of the substrate. A triad of polar residues in the second‐shell is found to modulate the highly conserved chitinase active site. As a novel target for asthma therapy, structural details of AMCase activity will help guide the future design of specific and potent AMCase inhibitors. |
| doi_str_mv | 10.1002/pro.63 |
| format | Article |
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One of only two active mammalian chinases, AMCase, is distinguished from other chitinases by several unique features. Here, we present the novel structure of the AMCase catalytic domain, both in the apo form and in complex with the inhibitor methylallosamidin, determined to high resolution by X‐ray crystallography. These results provide a structural basis for understanding some of the unique characteristics of this enzyme, including the low pH optimum and the preference for the β‐anomer of the substrate. A triad of polar residues in the second‐shell is found to modulate the highly conserved chitinase active site. As a novel target for asthma therapy, structural details of AMCase activity will help guide the future design of specific and potent AMCase inhibitors.</description><identifier>ISSN: 0961-8368</identifier><identifier>EISSN: 1469-896X</identifier><identifier>DOI: 10.1002/pro.63</identifier><identifier>PMID: 19241384</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>3D‐structure ; Acetylglucosamine - analogs & derivatives ; Acetylglucosamine - metabolism ; Amino Acid Sequence ; Animals ; asthma ; Asthma - metabolism ; Catalytic Domain - physiology ; chitin degradation ; chitinase ; Chitinases - chemistry ; Chitinases - genetics ; Chitinases - metabolism ; CHO Cells ; Cricetinae ; Cricetulus ; crystallography ; Crystallography, X-Ray ; Humans ; Hydrogen-Ion Concentration ; inhibitor ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; structure ; Substrate Specificity - physiology ; Trisaccharides - metabolism</subject><ispartof>Protein science, 2009-03, Vol.18 (3), p.569-578</ispartof><rights>Copyright © 2009 The Protein Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4643-7769ab2140a179a853a568a1585d408007b11ae785afb77acbc2b485b7229acf3</citedby><cites>FETCH-LOGICAL-c4643-7769ab2140a179a853a568a1585d408007b11ae785afb77acbc2b485b7229acf3</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/PMC2760363/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760363/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19241384$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olland, Andrea M.</creatorcontrib><creatorcontrib>Strand, James</creatorcontrib><creatorcontrib>Presman, Eleonora</creatorcontrib><creatorcontrib>Czerwinski, Robert</creatorcontrib><creatorcontrib>Joseph‐McCarthy, Diane</creatorcontrib><creatorcontrib>Krykbaev, Rustem</creatorcontrib><creatorcontrib>Schlingmann, Gerhard</creatorcontrib><creatorcontrib>Chopra, Rajiv</creatorcontrib><creatorcontrib>Lin, Laura</creatorcontrib><creatorcontrib>Fleming, Margaret</creatorcontrib><creatorcontrib>Kriz, Ron</creatorcontrib><creatorcontrib>Stahl, Mark</creatorcontrib><creatorcontrib>Somers, William</creatorcontrib><creatorcontrib>Fitz, Lori</creatorcontrib><creatorcontrib>Mosyak, Lidia</creatorcontrib><title>Triad of polar residues implicated in pH specificity of acidic mammalian chitinase</title><title>Protein science</title><addtitle>Protein Sci</addtitle><description>Acidic mammalian chitinase (AMCase) is a mammalian chitinase that has been implicated in allergic asthma. One of only two active mammalian chinases, AMCase, is distinguished from other chitinases by several unique features. Here, we present the novel structure of the AMCase catalytic domain, both in the apo form and in complex with the inhibitor methylallosamidin, determined to high resolution by X‐ray crystallography. These results provide a structural basis for understanding some of the unique characteristics of this enzyme, including the low pH optimum and the preference for the β‐anomer of the substrate. A triad of polar residues in the second‐shell is found to modulate the highly conserved chitinase active site. As a novel target for asthma therapy, structural details of AMCase activity will help guide the future design of specific and potent AMCase inhibitors.</description><subject>3D‐structure</subject><subject>Acetylglucosamine - analogs & derivatives</subject><subject>Acetylglucosamine - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>asthma</subject><subject>Asthma - metabolism</subject><subject>Catalytic Domain - physiology</subject><subject>chitin degradation</subject><subject>chitinase</subject><subject>Chitinases - chemistry</subject><subject>Chitinases - genetics</subject><subject>Chitinases - metabolism</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>crystallography</subject><subject>Crystallography, X-Ray</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>inhibitor</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Protein Conformation</subject><subject>structure</subject><subject>Substrate Specificity - physiology</subject><subject>Trisaccharides - metabolism</subject><issn>0961-8368</issn><issn>1469-896X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1r3DAQhkVpSDZp-hOKToUcnEiWrI9LoSz5KAQSlg30Jsay3EyxLVfypuy_j9MsTXLIaRjm4ZmZl5DPnJ1yxsqzMcVTJT6QBZfKFsaqnx_JglnFCyOUOSCHOf9mjElein1ywG0puTByQVbrhNDQ2NIxdpBoChmbTcgU-7FDD1NoKA50vKJ5DB5b9Dhtn3Dw2KCnPfQ9dAgD9fc44QA5fCJ7LXQ5HO_qEbm7OF8vr4rrm8sfy-_XhZdKikJrZaEuuWTAtQVTCaiUAV6ZqpHMMKZrziFoU0Fbaw2-9mUtTVXrsrTgW3FEvj17x03dh8aHYUrQuTFhD2nrIqB7Oxnw3v2KD67UigklZsHXnSDFP_PPk-sx-9B1MIS4yU4pa6wwr0CfYs4ptP-XcOae4p_76P4Zv7w-6QXb5T0DJ8_AX-zC9h2Nu13dzLJHcT6O_A</recordid><startdate>200903</startdate><enddate>200903</enddate><creator>Olland, Andrea M.</creator><creator>Strand, James</creator><creator>Presman, Eleonora</creator><creator>Czerwinski, Robert</creator><creator>Joseph‐McCarthy, Diane</creator><creator>Krykbaev, Rustem</creator><creator>Schlingmann, Gerhard</creator><creator>Chopra, Rajiv</creator><creator>Lin, Laura</creator><creator>Fleming, Margaret</creator><creator>Kriz, Ron</creator><creator>Stahl, Mark</creator><creator>Somers, William</creator><creator>Fitz, Lori</creator><creator>Mosyak, Lidia</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>5PM</scope></search><sort><creationdate>200903</creationdate><title>Triad of polar residues implicated in pH specificity of acidic mammalian chitinase</title><author>Olland, Andrea M. ; Strand, James ; Presman, Eleonora ; Czerwinski, Robert ; Joseph‐McCarthy, Diane ; Krykbaev, Rustem ; Schlingmann, Gerhard ; Chopra, Rajiv ; Lin, Laura ; Fleming, Margaret ; Kriz, Ron ; Stahl, Mark ; Somers, William ; Fitz, Lori ; Mosyak, Lidia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4643-7769ab2140a179a853a568a1585d408007b11ae785afb77acbc2b485b7229acf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>3D‐structure</topic><topic>Acetylglucosamine - analogs & derivatives</topic><topic>Acetylglucosamine - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>asthma</topic><topic>Asthma - metabolism</topic><topic>Catalytic Domain - physiology</topic><topic>chitin degradation</topic><topic>chitinase</topic><topic>Chitinases - chemistry</topic><topic>Chitinases - genetics</topic><topic>Chitinases - metabolism</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>crystallography</topic><topic>Crystallography, X-Ray</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>inhibitor</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Protein Conformation</topic><topic>structure</topic><topic>Substrate Specificity - physiology</topic><topic>Trisaccharides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olland, Andrea M.</creatorcontrib><creatorcontrib>Strand, James</creatorcontrib><creatorcontrib>Presman, Eleonora</creatorcontrib><creatorcontrib>Czerwinski, Robert</creatorcontrib><creatorcontrib>Joseph‐McCarthy, Diane</creatorcontrib><creatorcontrib>Krykbaev, Rustem</creatorcontrib><creatorcontrib>Schlingmann, Gerhard</creatorcontrib><creatorcontrib>Chopra, Rajiv</creatorcontrib><creatorcontrib>Lin, Laura</creatorcontrib><creatorcontrib>Fleming, Margaret</creatorcontrib><creatorcontrib>Kriz, Ron</creatorcontrib><creatorcontrib>Stahl, Mark</creatorcontrib><creatorcontrib>Somers, William</creatorcontrib><creatorcontrib>Fitz, Lori</creatorcontrib><creatorcontrib>Mosyak, Lidia</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>PubMed Central (Full Participant titles)</collection><jtitle>Protein science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olland, Andrea M.</au><au>Strand, James</au><au>Presman, Eleonora</au><au>Czerwinski, Robert</au><au>Joseph‐McCarthy, Diane</au><au>Krykbaev, Rustem</au><au>Schlingmann, Gerhard</au><au>Chopra, Rajiv</au><au>Lin, Laura</au><au>Fleming, Margaret</au><au>Kriz, Ron</au><au>Stahl, Mark</au><au>Somers, William</au><au>Fitz, Lori</au><au>Mosyak, Lidia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Triad of polar residues implicated in pH specificity of acidic mammalian chitinase</atitle><jtitle>Protein science</jtitle><addtitle>Protein Sci</addtitle><date>2009-03</date><risdate>2009</risdate><volume>18</volume><issue>3</issue><spage>569</spage><epage>578</epage><pages>569-578</pages><issn>0961-8368</issn><eissn>1469-896X</eissn><abstract>Acidic mammalian chitinase (AMCase) is a mammalian chitinase that has been implicated in allergic asthma. One of only two active mammalian chinases, AMCase, is distinguished from other chitinases by several unique features. Here, we present the novel structure of the AMCase catalytic domain, both in the apo form and in complex with the inhibitor methylallosamidin, determined to high resolution by X‐ray crystallography. These results provide a structural basis for understanding some of the unique characteristics of this enzyme, including the low pH optimum and the preference for the β‐anomer of the substrate. A triad of polar residues in the second‐shell is found to modulate the highly conserved chitinase active site. As a novel target for asthma therapy, structural details of AMCase activity will help guide the future design of specific and potent AMCase inhibitors.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19241384</pmid><doi>10.1002/pro.63</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3D‐structure Acetylglucosamine - analogs & derivatives Acetylglucosamine - metabolism Amino Acid Sequence Animals asthma Asthma - metabolism Catalytic Domain - physiology chitin degradation chitinase Chitinases - chemistry Chitinases - genetics Chitinases - metabolism CHO Cells Cricetinae Cricetulus crystallography Crystallography, X-Ray Humans Hydrogen-Ion Concentration inhibitor Models, Molecular Molecular Sequence Data Protein Conformation structure Substrate Specificity - physiology Trisaccharides - metabolism |
| title | Triad of polar residues implicated in pH specificity of acidic mammalian chitinase |
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