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==Crystal Structure of Agd31B, alpha-transglucosylase in Glycoside Hydrolase Family 31, in complex with noncovalent Cyclophellitol Sulfamidate probe KK131==
==Crystal Structure of Agd31B, alpha-transglucosylase in Glycoside Hydrolase Family 31, in complex with noncovalent Cyclophellitol Sulfamidate probe KK131==
<StructureSection load='7p4c' size='340' side='right'caption='[[7p4c]]' scene=''>
<StructureSection load='7p4c' size='340' side='right'caption='[[7p4c]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P4C FirstGlance]. <br>
<table><tr><td colspan='2'>[[7p4c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P4C FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7p4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p4c OCA], [https://pdbe.org/7p4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p4c RCSB], [https://www.ebi.ac.uk/pdbsum/7p4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p4c ProSAT]</span></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5OV:(3aR,4S,5S,6R,7R,7aS)-7-(hydroxymethyl)-2,2-bis(oxidanylidene)-3a,4,5,6,7,7a-hexahydro-3H-benzo[d][1,2,3]oxathiazole-4,5,6-triol'>5OV</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7p4d|7p4d]], [[7p2z|7p2z]], [[7p32|7p32]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Oligosaccharide_4-alpha-D-glucosyltransferase Oligosaccharide 4-alpha-D-glucosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.161 2.4.1.161] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7p4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p4c OCA], [https://pdbe.org/7p4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p4c RCSB], [https://www.ebi.ac.uk/pdbsum/7p4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p4c ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/OL4AG_CELJU OL4AG_CELJU]] Alpha-transglucosylase that specifically transfers single glucosyl units from alpha(1->4)-glucans to the non-reducing terminal 4-OH of glucose and alpha(1->4)- and alpha(1->6)-linked glucosyl residues. Acts on amylose, amylopectin, glycogen and maltooligosaccharides, with the highest activity with maltotriose as a donor, and also accepts maltose. Does not act as a hydrolase: weak hydrolysis activity is only observed on the disaccharide maltose.<ref>PMID:23132856</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
alpha-Glucosidase inhibitors are potential therapeutics for the treatment of diabetes, viral infections, and Pompe disease. Herein, we report a 1,6-epi-cyclophellitol cyclosulfamidate as a new class of reversible alpha-glucosidase inhibitors that displays enzyme inhibitory activity by virtue of its conformational mimicry of the substrate when bound in the Michaelis complex. The alpha-d-glc-configured cyclophellitol cyclosulfamidate 4 binds in a competitive manner the human lysosomal acid alpha-glucosidase (GAA), ER alpha-glucosidases, and, at higher concentrations, intestinal alpha-glucosidases, displaying an excellent selectivity over the human beta-glucosidases GBA and GBA2 and glucosylceramide synthase (GCS). Cyclosulfamidate 4 stabilizes recombinant human GAA (rhGAA, alglucosidase alfa, Myozyme) in cell medium and plasma and facilitates enzyme trafficking to lysosomes. It stabilizes rhGAA more effectively than existing small-molecule chaperones and does so in vitro, in cellulo, and in vivo in zebrafish, thus representing a promising therapeutic alternative to Miglustat for Pompe disease.
1,6-epi-Cyclophellitol Cyclosulfamidate Is a Bona Fide Lysosomal alpha-Glucosidase Stabilizer for the Treatment of Pompe Disease.,Kok K, Kuo CL, Katzy RE, Lelieveld LT, Wu L, Roig-Zamboni V, van der Marel GA, Codee JDC, Sulzenbacher G, Davies GJ, Overkleeft HS, Aerts JMFG, Artola M J Am Chem Soc. 2022 Aug 17;144(32):14819-14827. doi: 10.1021/jacs.2c05666. Epub, 2022 Aug 2. PMID:35917590<ref>PMID:35917590</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7p4c" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Davies GJ]]
[[Category: Oligosaccharide 4-alpha-D-glucosyltransferase]]
[[Category: Wu L]]
[[Category: Davies, G J]]
[[Category: Wu, L]]
[[Category: Carbohydrate]]
[[Category: Gh31]]
[[Category: Glycoside hydrolase]]
[[Category: Hydrolase]]
[[Category: Inhibitor]]
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