6s24: Difference between revisions
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<StructureSection load='6s24' size='340' side='right'caption='[[6s24]], [[Resolution|resolution]] 2.12Å' scene=''> | <StructureSection load='6s24' size='340' side='right'caption='[[6s24]], [[Resolution|resolution]] 2.12Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6s24]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S24 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S24 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6s24]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Poephila_guttata Poephila guttata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S24 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6S24 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</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"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NGA:N-ACETYL-D-GALACTOSAMINE'>NGA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GALNT3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=59729 Poephila guttata])</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=6s24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s24 OCA], [http://pdbe.org/6s24 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s24 RCSB], [http://www.ebi.ac.uk/pdbsum/6s24 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s24 ProSAT]</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=6s24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s24 OCA], [http://pdbe.org/6s24 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s24 RCSB], [http://www.ebi.ac.uk/pdbsum/6s24 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s24 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Polypeptide GalNAc-transferase T3 (GalNAc-T3) regulates fibroblast growth factor 23 (FGF23) by O-glycosylating Thr178 in a furin proprotein processing motif RHT(178)R downward arrowS. FGF23 regulates phosphate homeostasis and deficiency in GALNT3 or FGF23 results in hyperphosphatemia and familial tumoral calcinosis. We explored the molecular mechanism for GalNAc-T3 glycosylation of FGF23 using engineered cell models and biophysical studies including kinetics, molecular dynamics and X-ray crystallography of GalNAc-T3 complexed to glycopeptide substrates. GalNAc-T3 uses a lectin domain mediated mechanism to glycosylate Thr178 requiring previous glycosylation at Thr171. Notably, Thr178 is a poor substrate site with limiting glycosylation due to substrate clashes leading to destabilization of the catalytic domain flexible loop. We suggest GalNAc-T3 specificity for FGF23 and its ability to control circulating levels of intact FGF23 is achieved by FGF23 being a poor substrate. GalNAc-T3's structure further reveals the molecular bases for reported disease-causing mutations. Our findings provide an insight into how GalNAc-T isoenzymes achieve isoenzyme-specific nonredundant functions. | |||
Molecular basis for fibroblast growth factor 23 O-glycosylation by GalNAc-T3.,de Las Rivas M, Paul Daniel EJ, Narimatsu Y, Companon I, Kato K, Hermosilla P, Thureau A, Ceballos-Laita L, Coelho H, Bernado P, Marcelo F, Hansen L, Maeda R, Lostao A, Corzana F, Clausen H, Gerken TA, Hurtado-Guerrero R Nat Chem Biol. 2020 Jan 13. pii: 10.1038/s41589-019-0444-x. doi:, 10.1038/s41589-019-0444-x. PMID:31932717<ref>PMID:31932717</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6s24" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Poephila guttata]] | |||
[[Category: Bernado, P]] | [[Category: Bernado, P]] | ||
[[Category: Ceballos-Laita, L]] | [[Category: Ceballos-Laita, L]] | ||
