4d0t: Difference between revisions
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The | ==GalNAc-T2 crystal soaked with UDP-GalNAc, EA2 peptide and manganese== | ||
<StructureSection load='4d0t' size='340' side='right'caption='[[4d0t]], [[Resolution|resolution]] 2.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4d0t]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D0T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D0T 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]] 2.45Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene>, <scene name='pdbligand=UD2:URIDINE-DIPHOSPHATE-N-ACETYLGALACTOSAMINE'>UD2</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=4d0t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d0t OCA], [https://pdbe.org/4d0t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d0t RCSB], [https://www.ebi.ac.uk/pdbsum/4d0t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d0t ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== Publication Abstract from PubMed == | |||
The retaining glycosyltransferase GalNAc-T2 is a member of a large family of human polypeptide GalNAc-transferases that is responsible for the post-translational modification of many cell-surface proteins. By the use of combined structural and computational approaches, we provide the first set of structural snapshots of the enzyme during the catalytic cycle and combine these with quantum-mechanics/molecular-mechanics (QM/MM) metadynamics to unravel the catalytic mechanism of this retaining enzyme at the atomic-electronic level of detail. Our study provides a detailed structural rationale for an ordered bi-bi kinetic mechanism and reveals critical aspects of substrate recognition, which dictate the specificity for acceptor Thr versus Ser residues and enforce a front-face SN i-type reaction in which the substrate N-acetyl sugar substituent coordinates efficient glycosyl transfer. | |||
Substrate-Guided Front-Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N-Acetylgalactosaminyltransferase 2.,Lira-Navarrete E, Iglesias-Fernandez J, Zandberg WF, Companon I, Kong Y, Corzana F, Pinto BM, Clausen H, Peregrina JM, Vocadlo DJ, Rovira C, Hurtado-Guerrero R Angew Chem Int Ed Engl. 2014 Jun 20. doi: 10.1002/anie.201402781. PMID:24954443<ref>PMID:24954443</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4d0t" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Clausen H]] | |||
[[Category: Companon I]] | |||
[[Category: Corzana F]] | |||
[[Category: Hurtado-Guerrero R]] | |||
[[Category: Iglesias-Fernandez J]] | |||
[[Category: Kong Y]] | |||
[[Category: Lira-Navarrete E]] | |||
[[Category: Peregrina JM]] | |||
[[Category: Pinto BM]] | |||
[[Category: Rovira C]] | |||
[[Category: Vocadlo D]] | |||
[[Category: Zandberg WF]] | |||
Latest revision as of 15:18, 20 December 2023
GalNAc-T2 crystal soaked with UDP-GalNAc, EA2 peptide and manganeseGalNAc-T2 crystal soaked with UDP-GalNAc, EA2 peptide and manganese
Structural highlights
FunctionGALT2_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 PubMedThe retaining glycosyltransferase GalNAc-T2 is a member of a large family of human polypeptide GalNAc-transferases that is responsible for the post-translational modification of many cell-surface proteins. By the use of combined structural and computational approaches, we provide the first set of structural snapshots of the enzyme during the catalytic cycle and combine these with quantum-mechanics/molecular-mechanics (QM/MM) metadynamics to unravel the catalytic mechanism of this retaining enzyme at the atomic-electronic level of detail. Our study provides a detailed structural rationale for an ordered bi-bi kinetic mechanism and reveals critical aspects of substrate recognition, which dictate the specificity for acceptor Thr versus Ser residues and enforce a front-face SN i-type reaction in which the substrate N-acetyl sugar substituent coordinates efficient glycosyl transfer. Substrate-Guided Front-Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N-Acetylgalactosaminyltransferase 2.,Lira-Navarrete E, Iglesias-Fernandez J, Zandberg WF, Companon I, Kong Y, Corzana F, Pinto BM, Clausen H, Peregrina JM, Vocadlo DJ, Rovira C, Hurtado-Guerrero R Angew Chem Int Ed Engl. 2014 Jun 20. doi: 10.1002/anie.201402781. PMID:24954443[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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