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7aua
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7aua is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Cryo-EM structure of human exostosin-like 3 (EXTL3) in complex with UDP== |
| + | <StructureSection load='7aua' size='340' side='right'caption='[[7aua]], [[Resolution|resolution]] 2.93Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7aua]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUA FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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;'>[[7au2|7au2]]</div></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glucuronosyl-galactosyl-proteoglycan_4-alpha-N-_acetylglucosaminyltransferase Glucuronosyl-galactosyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.223 2.4.1.223] </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=7aua FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aua OCA], [https://pdbe.org/7aua PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aua RCSB], [https://www.ebi.ac.uk/pdbsum/7aua PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aua ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/EXTL3_HUMAN EXTL3_HUMAN]] Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome. The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/EXTL3_HUMAN EXTL3_HUMAN]] Glycosyltransferase which regulates the biosynthesis of heparan sulfate (HS). Important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs) (PubMed:28132690, PubMed:28148688). Required for the function of REG3A in regulating keratinocyte proliferation and differentiation (PubMed:22727489).<ref>PMID:22727489</ref> <ref>PMID:28132690</ref> <ref>PMID:28148688</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating beta-D-glucuronosyl and N-acetyl-alpha-D-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3's GT47 domain to transfer beta-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism. | ||
| - | + | The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis.,Wilson LFL, Dendooven T, Hardwick SW, Echevarria-Poza A, Tryfona T, Krogh KBRM, Chirgadze DY, Luisi BF, Logan DT, Mani K, Dupree P Nat Commun. 2022 Jun 8;13(1):3314. doi: 10.1038/s41467-022-31048-2. PMID:35676258<ref>PMID:35676258</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7aua" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Glucuronosyl-galactosyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Chirgadze, D Y]] | ||
| + | [[Category: Dendooven, T]] | ||
| + | [[Category: Dupree, P]] | ||
| + | [[Category: Hardwick, S W]] | ||
| + | [[Category: Logan, D T]] | ||
| + | [[Category: Luisi, B F]] | ||
| + | [[Category: Mani, K]] | ||
| + | [[Category: Wilson, L F.L]] | ||
| + | [[Category: Glycosyltransferase]] | ||
| + | [[Category: Heparan]] | ||
| + | [[Category: N-acetylglucosaminyltransferase]] | ||
| + | [[Category: Transferase]] | ||
Current revision
Cryo-EM structure of human exostosin-like 3 (EXTL3) in complex with UDP
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Categories: Glucuronosyl-galactosyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferase | Large Structures | Chirgadze, D Y | Dendooven, T | Dupree, P | Hardwick, S W | Logan, D T | Luisi, B F | Mani, K | Wilson, L F.L | Glycosyltransferase | Heparan | N-acetylglucosaminyltransferase | Transferase
