CAZypedia - User contributions [en-ca]

https://www.cazypedia.org/api.php?action=feedcontributions&feedformat=atom&user=Mslwebmin CAZypedia - User contributions [en-ca] 2026-05-03T22:21:39Z User contributions MediaWiki 1.35.10 https://www.cazypedia.org/index.php?title=User:Mslwebmin&diff=16803 User:Mslwebmin 2022-01-10T23:13:17Z

<p>Mslwebmin: </p> <hr /> <div><cite>1</cite><br /> <br /> <br /> == References ==<br /> <biblio><br /> #1 isbn=9780444823304<br /> </biblio></div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Mslwebmin&diff=16802 User:Mslwebmin 2022-01-10T23:11:01Z

<p>Mslwebmin: </p> <hr /> <div><cite>McCarterWithers1994 YipWithers2006 VocadloDavies2008 Lairson2008</cite>.<br /> <br /> == References ==<br /> <biblio><br /> #McCarterWithers1994 pmid=7712292<br /> #YipWithers2006 pmid=16495121<br /> #VocadloDavies2008 pmid=18558099<br /> #Lairson2008 pmid=18518825<br /> </biblio></div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Karen_Eddy&diff=16440 User:Karen Eddy 2021-12-17T00:54:36Z

<p>Mslwebmin: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"</p> <hr /> <div>This is the user page of Karen Eddy. I'm a computer science student at UBC, currently (Summer 2012) working with [[User:Harry Brumer|Harry Brumer]] on the migration and improvement of ''CAZypedia''. In particular, I have re-coded the Biblio extension to make it more efficient and resolve issues due to non-English characters in [http://www.ncbi.nlm.nih.gov/pubmed/ PubMed] [http://www.ncbi.nlm.nih.gov/books/NBK25501/ bibliographic data]. The result, [http://www.mediawiki.org/wiki/Extension:BiblioPlus BiblioPlus], is freely available for use with any Mediawiki installation from the [http://www.mediawiki.org/wiki/Extension:BiblioPlus MediaWiki Extensions repository].<br /> <br /> <br /> [[Category:Contributors|Eddy, Karen]]</div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Mslwebmin&diff=16439 User:Mslwebmin 2021-12-17T00:38:17Z

<p>Mslwebmin: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"</p> <hr /> <div>I work for [[User:Harry Brumer|Harry Brumer]]</div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Mslwebmin&diff=16438 User:Mslwebmin 2021-12-17T00:06:35Z

<p>Mslwebmin: </p> <hr /> <div>I work for ^^^Harry Brumer^^^</div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Mslwebmin&diff=16437 User:Mslwebmin 2021-12-17T00:04:36Z

<p>Mslwebmin: </p> <hr /> <div>I work for [[User:Harry Brumer]]<br /> I work for [[User:Harry_Brumer]]</div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Mslwebmin&diff=16436 User:Mslwebmin 2021-12-17T00:03:47Z

<p>Mslwebmin: Created page with "I work for Harry Brumer I work for Harry Brumer"</p> <hr /> <div>I work for [[User:Harry Brumer|Harry Brumer]]<br /> I work for [[User:Harry_Brumer|Harry Brumer]]</div>

Mslwebmin https://www.cazypedia.org/index.php?title=Lexicon&diff=16419 Lexicon 2021-12-11T09:03:50Z

<p>Mslwebmin: </p> <hr /> <div>The entries listed below comprise a lexicon of key terms and concepts in ''CAZypedia''. Specifically, the aim of the lexicon is to provide a precise definition of various specialized terms unique to carbohydrate chemistry <ref>StickWilliams2009 Sinnott2007 CollinsFerrier1995</ref>, as well as a general overview of the catalytic mechanisms of the major [[Carbohydrate-active enzymes|carbohydrate-active enzyme (CAZyme)]] classes <ref>Sinnott1990 McCarterWithers1994 YipWithers2006 VocadloDavies2008 Lairson2008</ref>.<br /> __TOC__<br /> <br /> == Curator Approved ==<br /> <blockquote class="toccolours" style="float:none; padding: 10px 15px 10px 15px; display:table;"><br /> [[Image:Approve_icon-50px.png|left]] These pages have been approved by the [[Responsible Curator]] as essentially complete. ''CAZypedia'' is a living document, so further improvement of these pages is still possible; please see the individual pages for more information.<br /> </blockquote><br /> {{#dpl:<br /> |category=Definitions and explanations<br /> |category=Curator approved<br /> |resultsheader=\nThere are currently %PAGES% [[:Category:Curator approved|Curator approved]] Lexicon pages in ''CAZypedia''.\n<br /> |noresultsheader=\nThere are currently no pages in this category.\n<br /> |ordermethod=sortkey<br /> |order=ascending<br /> |columns=3<br /> |rowcolformat=width=100%<br /> |redirects=exclude<br /> |allowcachedresults=no<br /> }}<br /> <br /> <br /> == Under construction ==<br /> <blockquote class="toccolours" style="float:none; padding: 10px 15px 10px 15px; display:table;"><br /> [[Image:Under_construction_icon-blue-48px.png|left]]These pages are currently [[:Category:Under construction|under construction]] in ''CAZypedia''. As such, the [[Responsible Curator]] has deemed that the page's content is not quite up to ''CAZypedia's'' standards for full public consumption. All information on these pages should therefore be considered to be under revision and may be subject to major changes.<br /> </blockquote><br /> {{#dpl:<br /> |category=Definitions and explanations<br /> |category=Under construction<br /> |resultsheader=\nThere are currently %PAGES% Lexicon pages [[:Category:Under construction|under construction]] in ''CAZypedia''.\n<br /> |noresultsheader=\nThere are currently no pages in this category.\n<br /> |ordermethod=sortkey<br /> |order=ascending<br /> |columns=3<br /> |rowcolformat=width=100%<br /> |redirects=exclude<br /> |allowcachedresults=no<br /> }}<br /> <br /> <br /> == References ==<br /> <biblio><br /> #StickWilliams2009 isbn=9780240521183<br /> #CollinsFerrier1995 isbn=0471953431<br /> #McCarterWithers1994 pmid=7712292<br /> #VocadloDavies2008 pmid=18558099<br /> #Sinnott1990 Sinnott, M.L. (1990) Catalytic mechanisms of enzymic glycosyl transfer. Chem. Rev. 90, 1171-1202. [http://dx.doi.org/10.1021/cr00105a006 DOI: 10.1021/cr00105a006]<br /> #Lairson2008 pmid=18518825<br /> #YipWithers2006 pmid=16495121<br /> #Sinnott2007 isbn=9780854042562<br /> </biblio></div>

Mslwebmin https://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Families&diff=16418 Glycoside Hydrolase Families 2021-12-11T09:00:31Z

<p>Mslwebmin: </p> <hr /> <div>''This page lists all the Glycoside Hydrolase (GH) Family pages in ''CAZypedia'' that have been given [[:Category:Curator approved|Curator Approved]] status, as well as those that are currently [[:Category:Under construction|under construction]], [[:Category:Unassigned pages|unassigned]] (''i.e.'' lacking a [[Responsible Curator]] and [[Author]]), or deleted.''<br /> <br /> == Overview ==<br /> The term [[glycoside hydrolase|glycoside hydrolase (GH)]] (''alternatively, [[glycoside hydrolase|glycosidase]]'') formally refers to enzymes that catalyze the hydrolytic cleavage of the glycosidic bond to give the carbohydrate hemiacetal. Detailed explanations of the distinct catalytic mechanisms employed by these enzymes can be found on the [[glycoside hydrolase]] lexicon page. Since the seminal [[sequence-based classification]] of GHs into families, it has subsequently been observed that some of these families also group non-hydrolytic enzymes and proteins, due to sequence and structural similarity <ref>Henrissat1989 Henrissat1991 Henrissat1993 Henrissat1996 Henrissat1997 DaviesSinnott2008 Davies1995 VocadloDavies2008 YipWithers2006</ref>. In many cases, these alternative activities bear some degree of mechanistic similarity (''e.g.'', conserved catalytic residues or enzyme intermediates) to the eponymous enzymes:<br /> <br /> * [[Transglycosylases]] are mechanistically related to [[retaining]] [[glycoside hydrolases]], with the exception that a sugar (or another nucleophile), rather than water, acts as the acceptor substrate to yield glycosidic bond exchange.<br /> <br /> * [[Phosphorylases]] cleave glycosidic bonds using phosphate as a nucleophile to yield sugar-1-phosphates; this reaction is readily reversible, allowing the synthesis of glycosidic linkages. Sequence classifies many, but not all (see [[glycosyltransferases]] for exceptions) [[phosphorylases]] with [[retaining]] or [[inverting]] [[glycoside hydrolases]].<br /> <br /> * [[Alpha-glucan lyases]] are found within family [[GH31]] and degrade &alpha;-(1-4)-linked glucans (''e.g.'' starch) and oligosaccharides via an elimination mechanism that yields an enol (unsaturated) product that tautomerises to its keto form, 1,5-anhydro fructose.<br /> <br /> * [[NAD-dependent hydrolysis|NAD-dependent glycoside hydrolases]] of families [[GH4]] and [[GH109]] use nicotinamide adenine dinucleotide as redox cofactor to activate the sugar ring for glycosidic bond cleavage by elimination.<br /> <br /> == Curator Approved ==<br /> <blockquote class="toccolours" style="float:none; padding: 10px 15px 10px 15px; display:table;"><br /> [[Image:Approve_icon-50px.png|left]] These pages have been approved by the [[Responsible Curator]] as essentially complete. ''CAZypedia'' is a living document, so further improvement of these pages is still possible; please see the individual pages for more information.<br /> </blockquote><br /> {{#dpl:<br /> |category=Glycoside Hydrolase Families<br /> |category=Curator approved<br /> |resultsheader=\nThere are currently %PAGES% [[:Category:Curator approved|Curator approved]] Glycoside Hydrolase (GH) Family pages in ''CAZypedia''.\n<br /> |noresultsheader=\nThere are currently no pages in this category.\n<br /> |ordermethod=sortkey<br /> |order=ascending<br /> |replaceintitle=/Glycoside Hydrolase Family /,GH<br /> |columns=10<br /> |rowcolformat=width=100%<br /> |allowcachedresults=no<br /> }}<br /> <br /> == Under construction ==<br /> <blockquote class="toccolours" style="float:none; padding: 10px 15px 10px 15px; display:table;"><br /> [[Image:Under_construction_icon-blue-48px.png|left]]These pages are currently [[:Category:Under construction|under construction]] in ''CAZypedia''. As such, the [[Responsible Curator]] has deemed that the page's content is not quite up to ''CAZypedia's'' standards for full public consumption. All information on these pages should therefore be considered to be under revision and may be subject to major changes.<br /> </blockquote><br /> {{#dpl:<br /> |category=Glycoside Hydrolase Families<br /> |category=Under construction<br /> |resultsheader=\nThere are currently %PAGES% Glycoside Hydrolase Family pages [[:Category:Under construction|under construction]] in ''CAZypedia''.\n<br /> |noresultsheader=\nThere are currently no pages in this category.\n<br /> |ordermethod=sortkey<br /> |order=ascending<br /> |replaceintitle=/Glycoside Hydrolase Family /,GH<br /> |columns=10<br /> |rowcolformat=width=100%<br /> |allowcachedresults=no<br /> }}<br /> <br /> == Unassigned pages ==<br /> <blockquote class="toccolours" style="float:none; padding: 10px 15px 10px 15px; display:table;"><br /> [[File:Blank user-200px.png|left|40px]]The following [[:Category:Unassigned pages|Unassigned pages]] are currently lacking a [[Responsible Curator]] and one or more [[Author]]s. If you are an expert on any of these families and would like to help us improve ''CAZypedia'' by getting involved with the production and maintenance of the corresponding page(s), please contact a member of the [[Board of Curators]]. ''Undergraduate students, (post)graduate students, post-doctoral researchers, research associates, and professors are all welcomed to contribute!''<br /> <br /> </blockquote><br /> {{#dpl:<br /> |category=Glycoside Hydrolase Families<br /> |category=Unassigned pages<br /> |resultsheader=\nThere are currently %PAGES% Glycoside Hydrolase Family pages in ''CAZypedia'' that have not been assigned to a [[Responsible Curator]].\n<br /> |noresultsheader=\nThere are currently no pages in this category.\n<br /> |ordermethod=sortkey<br /> |order=ascending<br /> |replaceintitle=/Glycoside Hydrolase Family /,GH<br /> |columns=10<br /> |rowcolformat=width=100%<br /> |allowcachedresults=no<br /> }}<br /> <br /> == Deleted families ==<br /> <blockquote class="toccolours" style="float:none; padding: 10px 15px 10px 15px; display:table;"><br /> [[File:Nuvola_apps_important.png|left|40px]]The following families have been deleted from the CAZy database. Please see the individual ''CAZypedia'' pages and links to the corresponding CAZy DB pages for specific explanations.<br /> </blockquote><br /> {{#dpl:<br /> |category=Glycoside Hydrolase Families<br /> |category=Deleted families<br /> |resultsheader=\nThere are currently %PAGES% pages in ''CAZypedia'' that describe Glycoside Hydrolase families deleted from the CAZy DB.\n<br /> |noresultsheader=\nThere are currently no pages in this category.\n<br /> |ordermethod=sortkey<br /> |order=ascending<br /> |replaceintitle=/Glycoside Hydrolase Family /,GH<br /> |columns=10<br /> |rowcolformat=width=100%<br /> |allowcachedresults=no<br /> }}<br /> <br /> == References ==<br /> <biblio><br /> #Henrissat1989 pmid=2806912<br /> #Henrissat1991 pmid=1747104<br /> <br /> #Henrissat1993 pmid=8352747<br /> #Henrissat1996 pmid=8687420<br /> #Davies1995 pmid=8535779<br /> #Henrissat1997 pmid=9345621<br /> #DaviesSinnott2008 Davies, G.J. and Sinnott, M.L. (2008) Sorting the diverse: the sequence-based classifications of carbohydrate-active enzymes. ''The Biochemist'', vol. 30, no. 4., pp. 26-32. [https://doi.org/10.1042/BIO03004026 Download PDF version].<br /> #VocadloDavies2008 pmid=18558099<br /> #YipWithers2006 pmid=16495121<br /> </biblio></div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Vtingey&diff=13442 User:Vtingey 2018-11-23T18:14:23Z

<p>Mslwebmin: Blanked the page</p> <hr /> <div></div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Vtingey&diff=13441 User:Vtingey 2018-11-23T17:54:56Z

<p>Mslwebmin: </p> <hr /> <div>test again by webmin<br /> <br /> test again by webmin<br /> test again by webmin<br /> test again by webmin<br /> test again by webmintest again by webmin<br /> <br /> test again by webmintest again by webmin<br /> test again by webmin<br /> test again by webmin</div>

Mslwebmin https://www.cazypedia.org/index.php?title=User:Vtingey&diff=13440 User:Vtingey 2018-11-23T17:50:10Z

<p>Mslwebmin: </p> <hr /> <div>test by webmin</div>

Mslwebmin https://www.cazypedia.org/index.php?title=MediaWiki:Common.js&diff=13052 MediaWiki:Common.js 2018-05-28T16:54:24Z

<p>Mslwebmin: </p> <hr /> <div>/* Any JavaScript here will be loaded for all users on every page load. */<br /> <br /> // install [[User:Cacycle/wikEd]] in-browser text editor<br /> //document.write('<script type="text/javascript" src="'<br /> //+ '//en.wikipedia.org/w/index.php?title=User:Cacycle/wikEd.js'<br /> //+ '&action=raw&ctype=text/javascript"></' + 'script>');<br /> <br /> // install [[:Wikipedia:User:Cacycle/wikEd]] in-browser text editor<br /> (function ()<br /> {<br /> var script = document.createElement('script');<br /> script.src = '//en.wikipedia.org/w/index.php?title=User:Cacycle/wikEd.js&action=raw&ctype=text/javascript';<br /> script.async = true;<br /> document.getElementsByTagName('head')[0].appendChild(script);<br /> }<br /> ) ();</div>

Mslwebmin https://www.cazypedia.org/index.php?title=MediaWiki:Common.js&diff=13004 MediaWiki:Common.js 2018-05-17T23:20:59Z

<p>Mslwebmin: </p> <hr /> <div>/* Any JavaScript here will be loaded for all users on every page load. */<br /> <br /> // install [[User:Cacycle/wikEd]] in-browser text editor<br /> //document.write('<script type="text/javascript" src="'<br /> //+ '//en.wikipedia.org/w/index.php?title=User:Cacycle/wikEd.js'<br /> //+ '&action=raw&ctype=text/javascript"></' + 'script>');</div>

Mslwebmin https://www.cazypedia.org/index.php?title=MediaWiki:Sitenotice&diff=11074 MediaWiki:Sitenotice 2016-06-09T16:51:31Z

<p>Mslwebmin: </p> <hr /> <div><span id="howToCite" style="color:darkgreen">''New to the CAZy classification? [http://www.biochemist.org/bio/03004/0026/030040026.pdf Read this first.]''</span></div>

Mslwebmin https://www.cazypedia.org/index.php?title=MediaWiki:Sitenotice&diff=11073 MediaWiki:Sitenotice 2016-06-08T16:18:10Z

<p>Mslwebmin: </p> <hr /> <div><span id="howToCite" style="color:darkgreen">''New to the CAZy classification? [http://www.biochemist.org/bio/03004/0026/030040026.pdf Read this first.]''</span><br /> <br /> <font color=red>Service Alert! The Cazypedia virtual server will be migrated from the UBC IT Virtual Server Service (VSS) to the newer EduCloud Server Service. Cazypedia will be offline temporarily for 5 – 15 minutes between 9:00am to 10:00am on Thursday, June 9th, 2016 PST. [amended]</font></div>

Mslwebmin https://www.cazypedia.org/index.php?title=MediaWiki:Sitenotice&diff=11072 MediaWiki:Sitenotice 2016-06-08T15:45:09Z

<p>Mslwebmin: </p> <hr /> <div><span id="howToCite" style="color:darkgreen">''New to the CAZy classification? [http://www.biochemist.org/bio/03004/0026/030040026.pdf Read this first.]''</span></div>

Mslwebmin https://www.cazypedia.org/index.php?title=Main_Page&diff=11069 Main Page 2016-06-07T22:15:56Z

<p>Mslwebmin: </p> <hr /> <div>__NOTOC__<br /> <br /> {| id="topbanner" style="width:100%; background:#fcfcfc; margin-top:1.2em; border:1px solid #ccc;"<br /> | style="width:60%; color:#000;" |<br /> <br /> {| style="width:100%; border:none; background:none;"<br /> | style="width:100%; text-align:center; white-space:nowrap; color:#000;" |<br /> <div style="font-size:160%; border:none; margin:0; padding:.1em; color:#000;">Welcome to ''CAZypedia!''</div><br /> <div style="top:+0.2em; font-size:100%;">The Encyclopedia of Carbohydrate-Active Enzymes.</div><br /> <div id="articlecount" style="width:100%; text-align:center; font-size:85%;"><br /> ''Now containing the following [[Curator Approved]] content:''<br><br /> {{CuratorApprovedGHPages}} [[Glycoside Hydrolase Families|Glycoside Hydrolase (GH) Family pages]],<br><br /> {{CuratorApprovedPLPages}} [[Polysaccharide Lyase Families|Polysaccharide Lyase (PL) Family pages]],<br><br /> {{CuratorApprovedAAPages}} [[Auxiliary Activity Families|Auxiliary Activity (AA) Family pages]],<br><br /> {{CuratorApprovedGTPages}} [[Glycosyltransferase Families|Glycosyltransferase (GT) Family pages]],<br><br /> {{CuratorApprovedCBMPages}} [[Carbohydrate Binding Module Families|Carbohydrate Binding Module (CBM) Family pages]],<br><br /> and<br><br /> {{CuratorApprovedLexiconPages}} [[Lexicon|Lexicon pages]]!<br /> <br /> <br /> <font color=red><br /> '''Service Alert!'''<br /> The Cazypedia virtual server will be migrated from the UBC IT Virtual Server Service (VSS) to the newer EduCloud Server Service. Cazypedia will be offline temporarily for 5 – 15 minutes starting at 5:45am on Wednesday, June 8th, 2016 PST.</font><br /> </div><br /> |}<br /> <br /> | style="width:40%; font-size:95%;"|<br /> [[Image:cazypedia_logo_big.png|right]]<br /> |}<br /> <br /> <br /> <br /> <br /> {| id="mp-upper" style="margin:0; background:none;"<br /> | id="MainPageBGLeft" style="width:60%; border:1px solid #cedff2; background:#f5faff; vertical-align:top; color:#000;" |<br /> {| id="mp-left" style="width:100%; vertical-align:top; background:#f5faff;"<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading1" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Purpose</h2><br /> |-<br /> | style="color:#000;" | <div id="LeftColumnText1" style="padding:2px 5px">{{Purpose}}</div><br /> |-<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading2" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Content</h2><br /> |-<br /> | style="color:#000;padding:2px 5px 5px" | <div id="LeftColumnText2">{{ContentDescriptionForMainPage}}</div><br /> |-<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading3" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">How ''CAZypedia'' works</h2><br /> |-<br /> | style="color:#000;padding:2px 5px 5px" | <div id="LeftColumnText3">{{HowCAZypediaWorks}}</div><br /> |-<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading4" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Contact</h2><br /> |-<br /> | style="color:#000;padding:2px 5px 5px" | <div id="LeftColumnText4">{{ContactInfoForMainPage}}</div><br /> |}<br /> | style="border:1px solid transparent;" |<br /> <br /> | id="MainPageBGRight" style="width:40%; border:1px solid #cedff2; background:#f5faff; vertical-align:top;"|<br /> {| id="mp-right" style="width:100%; vertical-align:top; background:#f5faff;"<br /> ! style="padding:2px" | <h2 id="RightColumnHeading3" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Latest news</h2><br /> |-<br /> | style="color:#000;font-size:95%;padding:2px 5px 5px" | <div id="RightColumnText2">{{News}}<small>[[News|''> older news'']]</small></div><br /> |}<br /> |}<br /> <br /> <br /> {| id="bottom" style="margin:4px 0 0 0; width:100%; background:none;"<br /> | class="MainPageBG" style="width:100%; border:1px solid #cedff2; background:#f5faff; vertical-align:top; color:#000;"|<br /> {| style="vertical-align:top; background:#f5faff; color:#000; width:100%"<br /> ! style="padding:2px" | <h2 id="mp-tfp-h2" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Dedication</h2><br /> |-<br /> | style="color:#000;padding: 2px 5px 5px" | ''CAZypedia'' is dedicated to the late [[Bruce Stone|Prof. Bruce Stone]], whose enthusiasm to create a comprehensive encyclopedia of carbohydrate-active enzymes was essential in the [[CAZypedia:History|genesis of this project]].<br /> |}<br /> |}</div>

Mslwebmin https://www.cazypedia.org/index.php?title=Main_Page&diff=11068 Main Page 2016-06-07T22:14:37Z

<p>Mslwebmin: </p> <hr /> <div>__NOTOC__<br /> <br /> {| id="topbanner" style="width:100%; background:#fcfcfc; margin-top:1.2em; border:1px solid #ccc;"<br /> | style="width:60%; color:#000;" |<br /> <br /> {| style="width:100%; border:none; background:none;"<br /> | style="width:100%; text-align:center; white-space:nowrap; color:#000;" |<br /> <div style="font-size:160%; border:none; margin:0; padding:.1em; color:#000;">Welcome to ''CAZypedia!''</div><br /> <div style="top:+0.2em; font-size:100%;">The Encyclopedia of Carbohydrate-Active Enzymes.</div><br /> <div id="articlecount" style="width:100%; text-align:center; font-size:85%;"><br /> ''Now containing the following [[Curator Approved]] content:''<br><br /> {{CuratorApprovedGHPages}} [[Glycoside Hydrolase Families|Glycoside Hydrolase (GH) Family pages]],<br><br /> {{CuratorApprovedPLPages}} [[Polysaccharide Lyase Families|Polysaccharide Lyase (PL) Family pages]],<br><br /> {{CuratorApprovedAAPages}} [[Auxiliary Activity Families|Auxiliary Activity (AA) Family pages]],<br><br /> {{CuratorApprovedGTPages}} [[Glycosyltransferase Families|Glycosyltransferase (GT) Family pages]],<br><br /> {{CuratorApprovedCBMPages}} [[Carbohydrate Binding Module Families|Carbohydrate Binding Module (CBM) Family pages]],<br><br /> and<br><br /> {{CuratorApprovedLexiconPages}} [[Lexicon|Lexicon pages]]!<br /> <br /> <br /> '''Service Alert!'''<br /> The Cazypedia virtual server will be migrated from the UBC IT Virtual Server Service (VSS) to the newer EduCloud Server Service. Cazypedia will be offline temporarily for 5 – 15 minutes starting at 5:45am on Wednesday, June 8th, 2016 PST.<br /> </div><br /> |}<br /> <br /> | style="width:40%; font-size:95%;"|<br /> [[Image:cazypedia_logo_big.png|right]]<br /> |}<br /> <br /> <br /> <br /> <br /> {| id="mp-upper" style="margin:0; background:none;"<br /> | id="MainPageBGLeft" style="width:60%; border:1px solid #cedff2; background:#f5faff; vertical-align:top; color:#000;" |<br /> {| id="mp-left" style="width:100%; vertical-align:top; background:#f5faff;"<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading1" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Purpose</h2><br /> |-<br /> | style="color:#000;" | <div id="LeftColumnText1" style="padding:2px 5px">{{Purpose}}</div><br /> |-<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading2" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Content</h2><br /> |-<br /> | style="color:#000;padding:2px 5px 5px" | <div id="LeftColumnText2">{{ContentDescriptionForMainPage}}</div><br /> |-<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading3" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">How ''CAZypedia'' works</h2><br /> |-<br /> | style="color:#000;padding:2px 5px 5px" | <div id="LeftColumnText3">{{HowCAZypediaWorks}}</div><br /> |-<br /> ! style="padding:2px" | <h2 id="LeftColumnHeading4" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Contact</h2><br /> |-<br /> | style="color:#000;padding:2px 5px 5px" | <div id="LeftColumnText4">{{ContactInfoForMainPage}}</div><br /> |}<br /> | style="border:1px solid transparent;" |<br /> <br /> | id="MainPageBGRight" style="width:40%; border:1px solid #cedff2; background:#f5faff; vertical-align:top;"|<br /> {| id="mp-right" style="width:100%; vertical-align:top; background:#f5faff;"<br /> ! style="padding:2px" | <h2 id="RightColumnHeading3" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Latest news</h2><br /> |-<br /> | style="color:#000;font-size:95%;padding:2px 5px 5px" | <div id="RightColumnText2">{{News}}<small>[[News|''> older news'']]</small></div><br /> |}<br /> |}<br /> <br /> <br /> {| id="bottom" style="margin:4px 0 0 0; width:100%; background:none;"<br /> | class="MainPageBG" style="width:100%; border:1px solid #cedff2; background:#f5faff; vertical-align:top; color:#000;"|<br /> {| style="vertical-align:top; background:#f5faff; color:#000; width:100%"<br /> ! style="padding:2px" | <h2 id="mp-tfp-h2" style="margin:3px; background:#cedff2; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; text-align:left; color:#000; padding:0.2em 0.4em;">Dedication</h2><br /> |-<br /> | style="color:#000;padding: 2px 5px 5px" | ''CAZypedia'' is dedicated to the late [[Bruce Stone|Prof. Bruce Stone]], whose enthusiasm to create a comprehensive encyclopedia of carbohydrate-active enzymes was essential in the [[CAZypedia:History|genesis of this project]].<br /> |}<br /> |}</div>

Mslwebmin https://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_47&diff=10627 Glycoside Hydrolase Family 47 2015-05-07T19:54:05Z

<p>Mslwebmin: </p> <hr /> <div>{{CuratorApproved}}<br /> <br /> * [[Author]]: ^^^Rohan Williams^^^<br /> * [[Responsible Curator]]: ^^^Spencer Williams^^^<br /> ----<br /> <br /> <br /> <div style="float:right"><br /> {| {{Prettytable}} <br /> |-<br /> |{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH47'''<br /> |-<br /> |'''Clan''' <br /> |none, (&alpha;/&alpha;)<sub>7</sub> fold<br /> |-<br /> |'''Mechanism'''<br /> |inverting<br /> |-<br /> |'''Active site residues'''<br /> |debated<br /> |-<br /> |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br /> |-<br /> | colspan="2" |{{CAZyDBlink}}GH47.html<br /> |}<br /> </div><br /> <br /> <br /> <br /> == Substrate specificities ==<br /> GH47 [[glycoside hydrolases]] are ''[[exo]]-acting ''&alpha;-1,2-mannosidases. Members from this family play important roles in the processing of N-glycans and are classified as Class I mannosidases; Class II mannosidases refer to those of family [[GH38]] <cite>Herscovics2001</cite>. Three subfamilies of GH47 enzymes have been identified based upon their different substrate specifities.<br /> <br /> In mammals, ER-&alpha;-mannosidase I (ERMI) is representative of the GH47 subfamily that acts upon Man<sub>9</sub>GlcNAc<sub>2</sub> to cleave a mannose from the B-chain to afford Man<sub>8</sub>GlcNAc<sub>2</sub>. Extended incubation results in further demannosylated products ''in vitro'' <cite>Tremblay2002</cite>, as does overexpression ''in vivo'' <cite>Nagata2003</cite>. Pulse-chase studies have found that ''Saccharomyces cerevisiae'' &alpha;-mannosidase I, the only GH47 mannosidase of the organism, bears essentially the same activity as mammalian ER-&alpha;-mannosidase I <cite>Herscovics2001</cite>.<br /> <br /> In mammals, the GH47 Golgi mannosidase I (Golgi MI) subfamily acts on Man<sub>8-9</sub>GlcNAc<sub>2</sub> to afford Man<sub>5</sub>GlcNAc<sub>2</sub> and is composed of 3 members (denoted IA, IB and IC) <cite>Herscovics2000</cite>. In contrast to mammalian ER-&alpha;-mannosidase I, the Golgi-resident GH47 mannosidases preferentially cleave from the A- and C-chains of the glycan in an order that depends on the subfamily member <cite>Moremen1998</cite>. All mammalian Golgi mannosidase I enzymes tested thus far have relatively low activity against the B-chain of the glycan, meaning that GH47 mannosidases from the ER and Golgi have complementary actitivities.<br /> <br /> The third GH47 subfamily is composed of the ER degradation-enhancing mannosidase-like (EDEM) proteins. This subfamily contains 3 members in humans and was initially believed to not have direct glycosidase activity. However, it now appears that the EDEM1 and EDEM3 isoforms have glycosidase activity ''in vivo'' <cite>Herscovics2010 Hosokawa2006</cite>. It has been suggested that the EDEM proteins act as cofactors, increasing the activity of ERMI <cite>Lederkremer2009</cite>. All of the EDEM isoforms accelerate the disposal of terminally misfolded proteins through ER-associated degradation (ERAD) <cite>Nagata2001 Hosokawa2006 Molinari2005</cite>. However, the process of recognition of terminally misfolded proteins and the role of EDEM proteins in ERAD is not fully understood. A current model for the early stages of ERAD states that correct folding mediated by the calnexin folding cycle must occur before the slow demannosylation of the substrate affords Man<sub>6</sub>GlcNAc<sub>2</sub>, which is no longer a substrate for reglucosylation by UGGT1 and re-entry into the calnexin folding cycle <cite>Lederkremer2009</cite>. It is not clear whether this extensive demannosylation is performed solely by ERMI ''in vivo'', which is found in high concentrations in the ER-derived quality control compartment, or if it is also performed by Golgi MI's and EDEM's.<br /> <br /> Fewer studies have focussed upon the role of GH47 enzymes in plants. However, it has been found that these mannosidases are essential for N-glycan processing in ''Arabidopsis thaliana'' <cite>Strasser2009</cite>.<br /> <br /> A bacterial GH47 enzyme from ''Caulobacter'' strain K31 was active on a range of aryl &alpha;-D-mannosides; its activity on N-glycans was not reported <cite>Davies2012</cite>.<br /> <br /> [[Image:GH47Figure1.png|thumb|900px|center|Schematic depicting the major modes of action of GH47 enzymes upon N-glycans in mammalian systems.]]<br /> <br /> == Kinetics and Mechanism ==<br /> GH47 mannosidases catalyze glycosidic cleavage with [[inverting|inversion]] of stereochemistry, as first determined employing <sup>1</sup>H NMR spectroscopy with ''Saccharomyces cervisiae'' &alpha;-1,2-mannosidase using Man<sub>9</sub>GlcNAc as a substrate <cite>Herscovics1995</cite>. Classical inverting glycosidases operate through a single displacement mechanism, where a [[general base]] residue acts to deprotonate a water molecule, facilitating nucleophilic attack at the anomeric position. This is assisted by concurrent activation of the glycosidic linkage through protonation by a [[general acid]] residue. <br /> <br /> GH47 enzymes are Ca<sup>2+</sup>-dependent, as demonstrated by loss of activity upon addition of the metal binding ligand EDTA, and restoration of activity through subsequent addition of Ca<sup>2+</sup> <cite>Herscovics1988</cite>. ''Exo''-&alpha;-mannosidases from [[GH38]] and [[GH92]] also require a metal ion for catalysis.<br /> <br /> GH47 mannosidases operate through an unusual <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary. Structural studies employing unhydrolysable S-linked substrate analogues have examined the Michaelis complex, with the ligands found to bind in <sup>3</sup>''S''<sub>1</sub> <cite>Moremen2005</cite> and <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub> conformations <cite>Davies2012</cite>. Mannoimidazole, whose binding to other mannosidases has been shown to be consistent with good transition state mimicry <cite>Davies2008</cite>, binds GH47 in a <sup>3</sup>''H''<sub>4</sub> conformation <cite>Davies2012</cite>. Noeuromycin <cite>Davies2012</cite>, kifunensine <cite>HowellJBC2000</cite> and 1-deoxymannojirimycin <cite>HowellJBC2000</cite> all bind in a <sup>1</sup>''C''<sub>4</sub> conformation, analogous to enzyme-product complexes. Computational studies also support a <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary <cite>Reilly2006 Reilly2007 Davies2012</cite>. Quantum mechanical/molecular modelling calculations have found that the free energy landscape of &alpha;-D-mannopyranose is perturbed on-enzyme such that the accessible conformations of the ligand are altered to those that correlate well with a <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary <cite>Davies2012</cite>.<br /> <br /> == Catalytic Residues ==<br /> Unequivocal assignment of catalytic residues for GH47 &alpha;-mannosidases is complicated by the presence of 3 carboxylate-containing residues all approximately 9.5 &Aring; apart from one another in the active site. Each of these could plausibly fulfill roles as catalytic residues <cite>Howell2000</cite>. Furthermore, all of the plausible catalytic residues complex water, as would be expected of the general base residue. Thus, it appears that the general acid residue transmits a proton to the glycosidic oxygen atom through a water molecule. Site-directed mutagenesis of residues in the &alpha;-mannosidase I of ''Aspergillus saitoi'' and ''Saccharomyces cerevisiae'' predated determination of a crystal structure but demonstrated that mutation of any of the three catalytic candidates led to total or near-total loss of activity <cite>Herscovics1999 Ischishima1997</cite>. Mutagenesis of residues in human ER &alpha;-mannosidase I, informed by the determination of the crystal structure, could not unambiguously assign the role of catalytic residues <cite>Moremen2005</cite>. Glu132 (Glu330 in human ER &alpha;-mannosidase I) in ''Saccharomyces cerevisiae'' &alpha;-mannosidase I was initially thought to be most likely candidate as the general base residue <cite>Howell2000</cite>. Subsequent crystal structures of human ER &alpha;-mannosidase I in complex with kifunensine and 1-deoxymannojirimycin bound these ligands in an unusual <sup>1</sup>''C''<sub>4</sub> conformation <cite>HowellJBC2000</cite>. These complexes were interpreted as being representative of a <sup>1</sup>''C''<sub>4</sub> Michaelis complex, making Glu330 (Glu132 in ''Saccharomyces'') incompatible with a role acting as the general base in an inverting mechanism. Thus, the general base residue was reassigned as either Glu599 or Asp463 (Glu435 and Asp275 in ''Saccharomyces'', respectively). A computational docking study found Glu599 to be the most likely general base, with Ca<sup>2+</sup> also coordinated to the nucleophilic water molecule <cite>Reilly2002</cite>. However, complexes with S-linked substrate analogues implicate a <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary, the reverse of that used to preclude Glu330 (Glu132 in ''Saccharomyces'') as the general base residue <cite>Moremen2005 Davies2012</cite>. The position of Glu330 (Glu132 in ''Saccharomyces'') on the opposite face of the glycan ring to the putative general base residue, Glu599 in human ER &alpha;-mannosidase I (Glu435 in ''Saccharomyces''), is consistent with a role as the general acid <cite>HowellJBC2000</cite>. Arg334 is within ion-pairing distance to Glu330 and coordinates to the same water molecule, suggestive of a possible catalytic zwitterionic arginine-carboxylate dyad <cite>Moremen2005</cite>. However, a computational docking study found Asp463 (Asp275 in ''Saccharomyces'') to be the most likely general acid, based upon the assumption that GH47 mannosidases are ''anti''-protonators <cite>Reilly2008</cite>. The low nanomolar binding of mannoimidazole to ''Ck''GH47 is consistent with ''anti''-protonation <cite>Davies2012</cite>.<br /> <br /> == Three-dimensional structures ==<br /> GH47 enzymes adopt a (&alpha;/&alpha;)<sub>7</sub> barrel fold with a Ca<sup>2+</sup> ion coordinated at the base of the barrel that is plugged by a &beta;-hairpin at the C-terminus <cite>Howell2000</cite>. The –1 subsite lies in the core of the barrel with Ca<sup>2+</sup> coordinating to the 2-OH and 3-OH groups of a ligand (inhibitor or substrate analogue), whose glycan ring is parallel to the barrel upon complexation <cite>HowellJBC2000</cite>.<br /> <br /> The structural basis for differences in N-glycan branch specificity between ER and Golgi GH47 &alpha;-mannosidases has been examined through crystallographic studies comparing their binding to N-glycans <cite>Moremen2004</cite>. The presumed enzyme-product complexes differed in their oligosaccharide conformation such that different oligosaccharide branches, corresponding to those readily cleaved by the respective enzymes, were projected into the active site.<br /> <br /> {| {{Prettytable}} <br /> |-<br /> <br /> !style="width:50%"|Three-dimensional structure of human GH47 &alpha;-mannosidase, PDB code [{{PDBlink}}1fmi] <cite>Herscovics2000</cite>. <br /> !style="width:50%"|Three-dimensional structure of human GH47 &alpha;-mannosidase in complex with 1-deoxymannojirimycin, PDB code [{{PDBlink}}1fo2] <cite>Herscovics2000</cite>.<br /> |-<br /> |<br /> <jmol><br /> <jmolApplet><br /> <color>white</color><br /> <frame>true</frame><br /> <uploadedFileContents>1FMI.pdb</uploadedFileContents><br /> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select ligand; wireframe 0.3; select MG; spacefill; set spin Y 10; spin off; set antialiasDisplay OFF</script><br /> </jmolApplet><br /> </jmol><br /> <br /> |<br /> <jmol><br /> <jmolApplet><br /> <color>white</color><br /> <frame>true</frame><br /> <uploadedFileContents>1FO2.pdb</uploadedFileContents><br /> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select DMJ; wireframe 0.3; set spin Y 10; spin off; set antialiasDisplay OFF</script><br /> </jmolApplet><br /> </jmol><br /> |-<br /> |}<br /> <br style="clear: both" /><br /> == Family Firsts ==<br /> ;First sterochemistry determination: ''Saccharomyces cerevisiae'' &alpha;-1,2-mannosidase was shown to be [[inverting]] by <sup>1</sup>H NMR <cite>Herscovics1995</cite>.<br /> ;First [[general base]] identification: Unambiguous identification hindered by presence of 3 carboxylate-containing residues in the active site that coordinate ligands through water molecules <cite>Howell2000</cite>. Believed to be Glu559 in human ER &alpha;-mannosidase I (Glu435 in ''S. cerevisiae'') <cite>Reilly2002</cite>.<br /> ;First [[general acid]] identification: Unambiguous identification hindered by presence of 3 carboxylate-containing residues in the active site that coordinate ligands through water molecules <cite>Howell2000</cite>. Reported to be Glu330 in human ER &alpha;-mannosidase I (Glu132 in ''S. cerevisiae'') <cite>HowellJBC2000</cite>, however, a computational study has concluded that Asp463 acts as the general acid in human ER &alpha;-mannosidase I (Asp275 in ''S. cerevisiae'') <cite>Reilly2008</cite>.<br /> ;First 3-D structure: ''Saccharomyces cerevisiae'' &alpha;-1,2-mannosidase <cite>Howell2000</cite>.<br /> <br /> == References ==<br /> <biblio><br /> #Moremen2004 pmid=15102839<br /> #Lederkremer2009 pmid=19616933<br /> #Nagata2003 pmid=12736254<br /> #Strasser2009 pmid=20023195<br /> #Tremblay2002 pmid=12090241<br /> #Nagata2001 pmid=11375934<br /> #Hosokawa2006 pmid=16431915<br /> #Herscovics2010 pmid=20065073<br /> #Molinari2005 pmid=15579471<br /> #Herscovics2000 pmid=10915796<br /> #Moremen1998 pmid=9719679<br /> #Herscovics2001 pmid=11530208<br /> #Ischishima1997 pmid=9325167<br /> #Davies2008 pmid=18408714<br /> #Herscovics1988 pmid=3049586<br /> #Herscovics1999 pmid=9894008<br /> #Herscovics1995 pmid=7726853<br /> #Moremen2005 pmid=15713668<br /> #Davies2012 pmid=23012075<br /> #Reilly2002 pmid=12211022<br /> #Reilly2006 pmid=16806128<br /> #Reilly2007 pmid=17157281<br /> #Reilly2008 pmid=18619586<br /> #HowellJBC2000 pmid=10995765<br /> #Howell2000 pmid=10675327<br /> <br /> </biblio><br /> <br /> [[Category:Glycoside Hydrolase Families|GH047]]</div>

Mslwebmin https://www.cazypedia.org/index.php?title=Glycoside_Hydrolase_Family_47&diff=10626 Glycoside Hydrolase Family 47 2015-05-07T19:53:52Z

<p>Mslwebmin: </p> <hr /> <div>TEST TEST TEST<br /> <br /> <br /> {{CuratorApproved}}<br /> <br /> * [[Author]]: ^^^Rohan Williams^^^<br /> * [[Responsible Curator]]: ^^^Spencer Williams^^^<br /> ----<br /> <br /> <br /> <div style="float:right"><br /> {| {{Prettytable}} <br /> |-<br /> |{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH47'''<br /> |-<br /> |'''Clan''' <br /> |none, (&alpha;/&alpha;)<sub>7</sub> fold<br /> |-<br /> |'''Mechanism'''<br /> |inverting<br /> |-<br /> |'''Active site residues'''<br /> |debated<br /> |-<br /> |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''<br /> |-<br /> | colspan="2" |{{CAZyDBlink}}GH47.html<br /> |}<br /> </div><br /> <br /> <br /> <br /> == Substrate specificities ==<br /> GH47 [[glycoside hydrolases]] are ''[[exo]]-acting ''&alpha;-1,2-mannosidases. Members from this family play important roles in the processing of N-glycans and are classified as Class I mannosidases; Class II mannosidases refer to those of family [[GH38]] <cite>Herscovics2001</cite>. Three subfamilies of GH47 enzymes have been identified based upon their different substrate specifities.<br /> <br /> In mammals, ER-&alpha;-mannosidase I (ERMI) is representative of the GH47 subfamily that acts upon Man<sub>9</sub>GlcNAc<sub>2</sub> to cleave a mannose from the B-chain to afford Man<sub>8</sub>GlcNAc<sub>2</sub>. Extended incubation results in further demannosylated products ''in vitro'' <cite>Tremblay2002</cite>, as does overexpression ''in vivo'' <cite>Nagata2003</cite>. Pulse-chase studies have found that ''Saccharomyces cerevisiae'' &alpha;-mannosidase I, the only GH47 mannosidase of the organism, bears essentially the same activity as mammalian ER-&alpha;-mannosidase I <cite>Herscovics2001</cite>.<br /> <br /> In mammals, the GH47 Golgi mannosidase I (Golgi MI) subfamily acts on Man<sub>8-9</sub>GlcNAc<sub>2</sub> to afford Man<sub>5</sub>GlcNAc<sub>2</sub> and is composed of 3 members (denoted IA, IB and IC) <cite>Herscovics2000</cite>. In contrast to mammalian ER-&alpha;-mannosidase I, the Golgi-resident GH47 mannosidases preferentially cleave from the A- and C-chains of the glycan in an order that depends on the subfamily member <cite>Moremen1998</cite>. All mammalian Golgi mannosidase I enzymes tested thus far have relatively low activity against the B-chain of the glycan, meaning that GH47 mannosidases from the ER and Golgi have complementary actitivities.<br /> <br /> The third GH47 subfamily is composed of the ER degradation-enhancing mannosidase-like (EDEM) proteins. This subfamily contains 3 members in humans and was initially believed to not have direct glycosidase activity. However, it now appears that the EDEM1 and EDEM3 isoforms have glycosidase activity ''in vivo'' <cite>Herscovics2010 Hosokawa2006</cite>. It has been suggested that the EDEM proteins act as cofactors, increasing the activity of ERMI <cite>Lederkremer2009</cite>. All of the EDEM isoforms accelerate the disposal of terminally misfolded proteins through ER-associated degradation (ERAD) <cite>Nagata2001 Hosokawa2006 Molinari2005</cite>. However, the process of recognition of terminally misfolded proteins and the role of EDEM proteins in ERAD is not fully understood. A current model for the early stages of ERAD states that correct folding mediated by the calnexin folding cycle must occur before the slow demannosylation of the substrate affords Man<sub>6</sub>GlcNAc<sub>2</sub>, which is no longer a substrate for reglucosylation by UGGT1 and re-entry into the calnexin folding cycle <cite>Lederkremer2009</cite>. It is not clear whether this extensive demannosylation is performed solely by ERMI ''in vivo'', which is found in high concentrations in the ER-derived quality control compartment, or if it is also performed by Golgi MI's and EDEM's.<br /> <br /> Fewer studies have focussed upon the role of GH47 enzymes in plants. However, it has been found that these mannosidases are essential for N-glycan processing in ''Arabidopsis thaliana'' <cite>Strasser2009</cite>.<br /> <br /> A bacterial GH47 enzyme from ''Caulobacter'' strain K31 was active on a range of aryl &alpha;-D-mannosides; its activity on N-glycans was not reported <cite>Davies2012</cite>.<br /> <br /> [[Image:GH47Figure1.png|thumb|900px|center|Schematic depicting the major modes of action of GH47 enzymes upon N-glycans in mammalian systems.]]<br /> <br /> == Kinetics and Mechanism ==<br /> GH47 mannosidases catalyze glycosidic cleavage with [[inverting|inversion]] of stereochemistry, as first determined employing <sup>1</sup>H NMR spectroscopy with ''Saccharomyces cervisiae'' &alpha;-1,2-mannosidase using Man<sub>9</sub>GlcNAc as a substrate <cite>Herscovics1995</cite>. Classical inverting glycosidases operate through a single displacement mechanism, where a [[general base]] residue acts to deprotonate a water molecule, facilitating nucleophilic attack at the anomeric position. This is assisted by concurrent activation of the glycosidic linkage through protonation by a [[general acid]] residue. <br /> <br /> GH47 enzymes are Ca<sup>2+</sup>-dependent, as demonstrated by loss of activity upon addition of the metal binding ligand EDTA, and restoration of activity through subsequent addition of Ca<sup>2+</sup> <cite>Herscovics1988</cite>. ''Exo''-&alpha;-mannosidases from [[GH38]] and [[GH92]] also require a metal ion for catalysis.<br /> <br /> GH47 mannosidases operate through an unusual <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary. Structural studies employing unhydrolysable S-linked substrate analogues have examined the Michaelis complex, with the ligands found to bind in <sup>3</sup>''S''<sub>1</sub> <cite>Moremen2005</cite> and <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub> conformations <cite>Davies2012</cite>. Mannoimidazole, whose binding to other mannosidases has been shown to be consistent with good transition state mimicry <cite>Davies2008</cite>, binds GH47 in a <sup>3</sup>''H''<sub>4</sub> conformation <cite>Davies2012</cite>. Noeuromycin <cite>Davies2012</cite>, kifunensine <cite>HowellJBC2000</cite> and 1-deoxymannojirimycin <cite>HowellJBC2000</cite> all bind in a <sup>1</sup>''C''<sub>4</sub> conformation, analogous to enzyme-product complexes. Computational studies also support a <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary <cite>Reilly2006 Reilly2007 Davies2012</cite>. Quantum mechanical/molecular modelling calculations have found that the free energy landscape of &alpha;-D-mannopyranose is perturbed on-enzyme such that the accessible conformations of the ligand are altered to those that correlate well with a <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary <cite>Davies2012</cite>.<br /> <br /> == Catalytic Residues ==<br /> Unequivocal assignment of catalytic residues for GH47 &alpha;-mannosidases is complicated by the presence of 3 carboxylate-containing residues all approximately 9.5 &Aring; apart from one another in the active site. Each of these could plausibly fulfill roles as catalytic residues <cite>Howell2000</cite>. Furthermore, all of the plausible catalytic residues complex water, as would be expected of the general base residue. Thus, it appears that the general acid residue transmits a proton to the glycosidic oxygen atom through a water molecule. Site-directed mutagenesis of residues in the &alpha;-mannosidase I of ''Aspergillus saitoi'' and ''Saccharomyces cerevisiae'' predated determination of a crystal structure but demonstrated that mutation of any of the three catalytic candidates led to total or near-total loss of activity <cite>Herscovics1999 Ischishima1997</cite>. Mutagenesis of residues in human ER &alpha;-mannosidase I, informed by the determination of the crystal structure, could not unambiguously assign the role of catalytic residues <cite>Moremen2005</cite>. Glu132 (Glu330 in human ER &alpha;-mannosidase I) in ''Saccharomyces cerevisiae'' &alpha;-mannosidase I was initially thought to be most likely candidate as the general base residue <cite>Howell2000</cite>. Subsequent crystal structures of human ER &alpha;-mannosidase I in complex with kifunensine and 1-deoxymannojirimycin bound these ligands in an unusual <sup>1</sup>''C''<sub>4</sub> conformation <cite>HowellJBC2000</cite>. These complexes were interpreted as being representative of a <sup>1</sup>''C''<sub>4</sub> Michaelis complex, making Glu330 (Glu132 in ''Saccharomyces'') incompatible with a role acting as the general base in an inverting mechanism. Thus, the general base residue was reassigned as either Glu599 or Asp463 (Glu435 and Asp275 in ''Saccharomyces'', respectively). A computational docking study found Glu599 to be the most likely general base, with Ca<sup>2+</sup> also coordinated to the nucleophilic water molecule <cite>Reilly2002</cite>. However, complexes with S-linked substrate analogues implicate a <sup>3,O</sup>''B''/<sup>3</sup>''S''<sub>1</sub>&rarr;<sup>3</sup>''H''<sub>4</sub><sup>‡</sup>&rarr;<sup>1</sup>''C''<sub>4</sub> conformational itinerary, the reverse of that used to preclude Glu330 (Glu132 in ''Saccharomyces'') as the general base residue <cite>Moremen2005 Davies2012</cite>. The position of Glu330 (Glu132 in ''Saccharomyces'') on the opposite face of the glycan ring to the putative general base residue, Glu599 in human ER &alpha;-mannosidase I (Glu435 in ''Saccharomyces''), is consistent with a role as the general acid <cite>HowellJBC2000</cite>. Arg334 is within ion-pairing distance to Glu330 and coordinates to the same water molecule, suggestive of a possible catalytic zwitterionic arginine-carboxylate dyad <cite>Moremen2005</cite>. However, a computational docking study found Asp463 (Asp275 in ''Saccharomyces'') to be the most likely general acid, based upon the assumption that GH47 mannosidases are ''anti''-protonators <cite>Reilly2008</cite>. The low nanomolar binding of mannoimidazole to ''Ck''GH47 is consistent with ''anti''-protonation <cite>Davies2012</cite>.<br /> <br /> == Three-dimensional structures ==<br /> GH47 enzymes adopt a (&alpha;/&alpha;)<sub>7</sub> barrel fold with a Ca<sup>2+</sup> ion coordinated at the base of the barrel that is plugged by a &beta;-hairpin at the C-terminus <cite>Howell2000</cite>. The –1 subsite lies in the core of the barrel with Ca<sup>2+</sup> coordinating to the 2-OH and 3-OH groups of a ligand (inhibitor or substrate analogue), whose glycan ring is parallel to the barrel upon complexation <cite>HowellJBC2000</cite>.<br /> <br /> The structural basis for differences in N-glycan branch specificity between ER and Golgi GH47 &alpha;-mannosidases has been examined through crystallographic studies comparing their binding to N-glycans <cite>Moremen2004</cite>. The presumed enzyme-product complexes differed in their oligosaccharide conformation such that different oligosaccharide branches, corresponding to those readily cleaved by the respective enzymes, were projected into the active site.<br /> <br /> {| {{Prettytable}} <br /> |-<br /> <br /> !style="width:50%"|Three-dimensional structure of human GH47 &alpha;-mannosidase, PDB code [{{PDBlink}}1fmi] <cite>Herscovics2000</cite>. <br /> !style="width:50%"|Three-dimensional structure of human GH47 &alpha;-mannosidase in complex with 1-deoxymannojirimycin, PDB code [{{PDBlink}}1fo2] <cite>Herscovics2000</cite>.<br /> |-<br /> |<br /> <jmol><br /> <jmolApplet><br /> <color>white</color><br /> <frame>true</frame><br /> <uploadedFileContents>1FMI.pdb</uploadedFileContents><br /> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select ligand; wireframe 0.3; select MG; spacefill; set spin Y 10; spin off; set antialiasDisplay OFF</script><br /> </jmolApplet><br /> </jmol><br /> <br /> |<br /> <jmol><br /> <jmolApplet><br /> <color>white</color><br /> <frame>true</frame><br /> <uploadedFileContents>1FO2.pdb</uploadedFileContents><br /> <script>cpk off; wireframe off; cartoon; color cartoon powderblue; select DMJ; wireframe 0.3; set spin Y 10; spin off; set antialiasDisplay OFF</script><br /> </jmolApplet><br /> </jmol><br /> |-<br /> |}<br /> <br style="clear: both" /><br /> == Family Firsts ==<br /> ;First sterochemistry determination: ''Saccharomyces cerevisiae'' &alpha;-1,2-mannosidase was shown to be [[inverting]] by <sup>1</sup>H NMR <cite>Herscovics1995</cite>.<br /> ;First [[general base]] identification: Unambiguous identification hindered by presence of 3 carboxylate-containing residues in the active site that coordinate ligands through water molecules <cite>Howell2000</cite>. Believed to be Glu559 in human ER &alpha;-mannosidase I (Glu435 in ''S. cerevisiae'') <cite>Reilly2002</cite>.<br /> ;First [[general acid]] identification: Unambiguous identification hindered by presence of 3 carboxylate-containing residues in the active site that coordinate ligands through water molecules <cite>Howell2000</cite>. Reported to be Glu330 in human ER &alpha;-mannosidase I (Glu132 in ''S. cerevisiae'') <cite>HowellJBC2000</cite>, however, a computational study has concluded that Asp463 acts as the general acid in human ER &alpha;-mannosidase I (Asp275 in ''S. cerevisiae'') <cite>Reilly2008</cite>.<br /> ;First 3-D structure: ''Saccharomyces cerevisiae'' &alpha;-1,2-mannosidase <cite>Howell2000</cite>.<br /> <br /> == References ==<br /> <biblio><br /> #Moremen2004 pmid=15102839<br /> #Lederkremer2009 pmid=19616933<br /> #Nagata2003 pmid=12736254<br /> #Strasser2009 pmid=20023195<br /> #Tremblay2002 pmid=12090241<br /> #Nagata2001 pmid=11375934<br /> #Hosokawa2006 pmid=16431915<br /> #Herscovics2010 pmid=20065073<br /> #Molinari2005 pmid=15579471<br /> #Herscovics2000 pmid=10915796<br /> #Moremen1998 pmid=9719679<br /> #Herscovics2001 pmid=11530208<br /> #Ischishima1997 pmid=9325167<br /> #Davies2008 pmid=18408714<br /> #Herscovics1988 pmid=3049586<br /> #Herscovics1999 pmid=9894008<br /> #Herscovics1995 pmid=7726853<br /> #Moremen2005 pmid=15713668<br /> #Davies2012 pmid=23012075<br /> #Reilly2002 pmid=12211022<br /> #Reilly2006 pmid=16806128<br /> #Reilly2007 pmid=17157281<br /> #Reilly2008 pmid=18619586<br /> #HowellJBC2000 pmid=10995765<br /> #Howell2000 pmid=10675327<br /> <br /> </biblio><br /> <br /> [[Category:Glycoside Hydrolase Families|GH047]]</div>

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