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| | <StructureSection load='5ajp' size='340' side='right'caption='[[5ajp]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='5ajp' size='340' side='right'caption='[[5ajp]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ajp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AJP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AJP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ajp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AJP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr> | + | </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=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ajn|5ajn]], [[5ajo|5ajo]]</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=5ajp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ajp OCA], [https://pdbe.org/5ajp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ajp RCSB], [https://www.ebi.ac.uk/pdbsum/5ajp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ajp ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polypeptide_N-acetylgalactosaminyltransferase Polypeptide N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.41 2.4.1.41] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ajp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ajp OCA], [http://pdbe.org/5ajp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ajp RCSB], [http://www.ebi.ac.uk/pdbsum/5ajp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ajp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GALT2_HUMAN GALT2_HUMAN]] 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. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.<ref>PMID:9295285</ref> <ref>PMID:12438318</ref> | + | [https://www.uniprot.org/uniprot/GALT2_HUMAN GALT2_HUMAN] 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. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.<ref>PMID:9295285</ref> <ref>PMID:12438318</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Polypeptide N-acetylgalactosaminyltransferase]]
| + | [[Category: Bernado P]] |
| - | [[Category: Bernado, P]] | + | [[Category: Bernardes GJL]] |
| - | [[Category: Bernardes, G J.L]] | + | [[Category: Bruscolini P]] |
| - | [[Category: Bruscolini, P]] | + | [[Category: Clausen H]] |
| - | [[Category: Clausen, H]] | + | [[Category: Companon I]] |
| - | [[Category: Companon, I]] | + | [[Category: Corzana F]] |
| - | [[Category: Corzana, F]] | + | [[Category: Hurtado-Guerrero R]] |
| - | [[Category: Hurtado-Guerrero, R]] | + | [[Category: Iglesias-Fernandez J]] |
| - | [[Category: Iglesias-Fernandez, J]] | + | [[Category: Kong Y]] |
| - | [[Category: Kong, Y]] | + | [[Category: Lira-Navarrete E]] |
| - | [[Category: Lira-Navarrete, E]] | + | [[Category: Lostao A]] |
| - | [[Category: Lostao, A]] | + | [[Category: Pallares MC]] |
| - | [[Category: Pallares, M C]] | + | [[Category: Peregrina JM]] |
| - | [[Category: Peregrina, J M]] | + | [[Category: Rovira C]] |
| - | [[Category: Rovira, C]] | + | [[Category: DelasRivas M]] |
| - | [[Category: DelasRivas, M]] | + | |
| - | [[Category: Active form]]
| + | |
| - | [[Category: Afm]]
| + | |
| - | [[Category: Coarse-grained model]]
| + | |
| - | [[Category: Compact form]]
| + | |
| - | [[Category: Extended form]]
| + | |
| - | [[Category: Galnac-t2]]
| + | |
| - | [[Category: Glycopeptide]]
| + | |
| - | [[Category: Inactive form]]
| + | |
| - | [[Category: Lectin domain]]
| + | |
| - | [[Category: Sax]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
GALT2_HUMAN 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. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.[1] [2]
Publication Abstract from PubMed
Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.
Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation.,Lira-Navarrete E, de Las Rivas M, Companon I, Pallares MC, Kong Y, Iglesias-Fernandez J, Bernardes GJ, Peregrina JM, Rovira C, Bernado P, Bruscolini P, Clausen H, Lostao A, Corzana F, Hurtado-Guerrero R Nat Commun. 2015 May 5;6:6937. doi: 10.1038/ncomms7937. PMID:25939779[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wandall HH, Hassan H, Mirgorodskaya E, Kristensen AK, Roepstorff P, Bennett EP, Nielsen PA, Hollingsworth MA, Burchell J, Taylor-Papadimitriou J, Clausen H. Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3. J Biol Chem. 1997 Sep 19;272(38):23503-14. PMID:9295285
- ↑ Iwasaki H, Zhang Y, Tachibana K, Gotoh M, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Kubota T, Narimatsu H. Initiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2. J Biol Chem. 2003 Feb 21;278(8):5613-21. Epub 2002 Nov 15. PMID:12438318 doi:http://dx.doi.org/10.1074/jbc.M211097200
- ↑ Lira-Navarrete E, de Las Rivas M, Companon I, Pallares MC, Kong Y, Iglesias-Fernandez J, Bernardes GJ, Peregrina JM, Rovira C, Bernado P, Bruscolini P, Clausen H, Lostao A, Corzana F, Hurtado-Guerrero R. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation. Nat Commun. 2015 May 5;6:6937. doi: 10.1038/ncomms7937. PMID:25939779 doi:http://dx.doi.org/10.1038/ncomms7937
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