4d0z: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==GalNAc-T2 crystal soaked with UDP-5SGalNAc, mEA2 and manganese (Higher resolution dataset)== | ==GalNAc-T2 crystal soaked with UDP-5SGalNAc, mEA2 and manganese (Higher resolution dataset)== | ||
<StructureSection load='4d0z' size='340' side='right' caption='[[4d0z]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='4d0z' size='340' side='right'caption='[[4d0z]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4d0z]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D0Z OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4d0z]] is a 8 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=4D0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D0Z FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBK:2-(ACETYLAMINO)-2-DEOXY-5-THIO-ALPHA-D-GALACTOPYRANOSE'>BBK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HWU:(2R,3R,4R,5R,6R)-3-( | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBK:2-(ACETYLAMINO)-2-DEOXY-5-THIO-ALPHA-D-GALACTOPYRANOSE'>BBK</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HWU:(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-thiopyran-2-yl+[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+dihydrogen+diphosphate+(non-preferred+name)'>HWU</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | |||
<tr | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4d0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d0z OCA], [https://pdbe.org/4d0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d0z RCSB], [https://www.ebi.ac.uk/pdbsum/4d0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d0z ProSAT]</span></td></tr> | ||
</table> | |||
<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 4d0z" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Clausen | [[Category: Large Structures]] | ||
[[Category: Companon | [[Category: Clausen H]] | ||
[[Category: Corzana | [[Category: Companon I]] | ||
[[Category: Hurtado-Guerrero | [[Category: Corzana F]] | ||
[[Category: Iglesias-Fernandez | [[Category: Hurtado-Guerrero R]] | ||
[[Category: Kong | [[Category: Iglesias-Fernandez J]] | ||
[[Category: Lira-Navarrete | [[Category: Kong Y]] | ||
[[Category: Peregrina | [[Category: Lira-Navarrete E]] | ||
[[Category: Pinto | [[Category: Peregrina JM]] | ||
[[Category: Rovira | [[Category: Pinto BM]] | ||
[[Category: Vocadlo | [[Category: Rovira C]] | ||
[[Category: Zandberg | [[Category: Vocadlo D]] | ||
[[Category: Zandberg WF]] | |||
Latest revision as of 11:24, 23 October 2024
GalNAc-T2 crystal soaked with UDP-5SGalNAc, mEA2 and manganese (Higher resolution dataset)GalNAc-T2 crystal soaked with UDP-5SGalNAc, mEA2 and manganese (Higher resolution dataset)
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
|
| ||||||||||||||||||