8v9q: Difference between revisions
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==Crystal structure of mGalNAc-T1 in complex with the mucin glycopeptide Muc5AC-13, Mn2+, and UDP.== | |||
<StructureSection load='8v9q' size='340' side='right'caption='[[8v9q]], [[Resolution|resolution]] 2.29Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8v9q]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8V9Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8V9Q FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></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=8v9q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8v9q OCA], [https://pdbe.org/8v9q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8v9q RCSB], [https://www.ebi.ac.uk/pdbsum/8v9q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8v9q ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GALT1_MOUSE GALT1_MOUSE] Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b and Muc7.<ref>PMID:9153242</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
N-acetylgalactosaminyl-transferases (GalNAc-Ts) initiate mucin-type O-glycosylation, an abundant and complex posttranslational modification that regulates host-microbe interactions, tissue development, and metabolism. GalNAc-Ts contain a lectin domain consisting of three homologous repeats (alpha, beta, and gamma), where alpha and beta can potentially interact with O-GalNAc on substrates to enhance activity toward a nearby acceptor Thr/Ser. The ubiquitous isoenzyme GalNAc-T1 modulates heart development, immunity, and SARS-CoV-2 infectivity, but its substrates are largely unknown. Here, we show that both alpha and beta in GalNAc-T1 uniquely orchestrate the O-glycosylation of various glycopeptide substrates. The alpha repeat directs O-glycosylation to acceptor sites carboxyl-terminal to an existing GalNAc, while the beta repeat directs O-glycosylation to amino-terminal sites. In addition, GalNAc-T1 incorporates alpha and beta into various substrate binding modes to cooperatively increase the specificity toward an acceptor site located between two existing O-glycans. Our studies highlight a unique mechanism by which dual lectin repeats expand substrate specificity and provide crucial information for identifying the biological substrates of GalNAc-T1. | |||
An unusual dual sugar-binding lectin domain controls the substrate specificity of a mucin-type O-glycosyltransferase.,Collette AM, Hassan SA, Schmidt SI, Lara AJ, Yang W, Samara NL Sci Adv. 2024 Mar;10(9):eadj8829. doi: 10.1126/sciadv.adj8829. Epub 2024 Feb 28. PMID:38416819<ref>PMID:38416819</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Collette | <div class="pdbe-citations 8v9q" style="background-color:#fffaf0;"></div> | ||
[[Category: Samara | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Collette AM]] | |||
[[Category: Samara NL]] | |||