4irp: Difference between revisions
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==Crystal structure of catalytic domain of human beta1,4-galactosyltransferase-7 in open conformation with manganses and UDP== | ==Crystal structure of catalytic domain of human beta1,4-galactosyltransferase-7 in open conformation with manganses and UDP== | ||
<StructureSection load='4irp' size='340' side='right' caption='[[4irp]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='4irp' size='340' side='right'caption='[[4irp]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4irp]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4irp]] 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=4IRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IRP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4irp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4irp OCA], [https://pdbe.org/4irp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4irp RCSB], [https://www.ebi.ac.uk/pdbsum/4irp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4irp ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/B4GT7_HUMAN B4GT7_HUMAN] Ehlers-Danlos syndrome, progeroid type. The disease is caused by mutations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/B4GT7_HUMAN B4GT7_HUMAN] Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 20: | ||
</div> | </div> | ||
<div class="pdbe-citations 4irp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4irp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Glycosyltransferase 3D structures|Glycosyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Qasba PK]] | ||
[[Category: | [[Category: Ramakrishnan B]] | ||
[[Category: | [[Category: Tsutsui Y]] | ||
Revision as of 00:06, 17 November 2022
Crystal structure of catalytic domain of human beta1,4-galactosyltransferase-7 in open conformation with manganses and UDPCrystal structure of catalytic domain of human beta1,4-galactosyltransferase-7 in open conformation with manganses and UDP
Structural highlights
DiseaseB4GT7_HUMAN Ehlers-Danlos syndrome, progeroid type. The disease is caused by mutations affecting the gene represented in this entry. FunctionB4GT7_HUMAN Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts. Publication Abstract from PubMedThe beta-1,4-galactosyltransferase 7 (beta4GalT7) enzyme is involved in proteoglycan synthesis. In the presence of a manganese ion, it transfers galactose from UDP-galactose to xylose on a proteoglycan acceptor substrate. We present here the crystal structures of human beta4GalT7 in open and closed conformations. A comparison of these crystal structures shows that, upon manganese and UDP or UDP-Gal binding, the enzyme undergoes conformational changes involving a small and a long loop. We also present the crystal structures of Drosophila wild-type beta4GalT7 and D211N beta4GalT7 mutant enzymes in the closed conformation in the presence of the acceptor substrate xylobiose and the donor substrate UDP-Gal, respectively. To understand the catalytic mechanism, we have crystallized the ternary complex of D211N beta4GalT7 mutant enzyme in the presence of manganese with the donor and the acceptor substrates together in the same crystal structure. The galactose moiety of the bound UDP-Gal molecule forms seven hydrogen bonds with the protein molecule. The nonreducing end of the xylose moiety of xylobiose binds to the hydrophobic acceptor sugar binding pocket created by the conformational changes, whereas its extended xylose moiety forms hydrophobic interactions with a Tyr residue. In the ternary complex crystal structure, the nucleophile O4 oxygen atom of the xylose molecule is found in close proximity to the C1 and O5 atoms of the galactose moiety. This is the first time that a Michaelis complex of a glycosyltransferase has been described, and it clearly suggests an SN2 type catalytic mechanism for the beta4GalT7 enzyme. Crystal Structures of beta-1,4-Galactosyltransferase 7 Enzyme Reveal Conformational Changes and Substrate Binding.,Tsutsui Y, Ramakrishnan B, Qasba PK J Biol Chem. 2013 Nov 1;288(44):31963-70. doi: 10.1074/jbc.M113.509984. Epub 2013, Sep 19. PMID:24052259[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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