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6s24

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Crystal structure of the TgGalNAc-T3 in complex with UDP, manganese and the peptide 3

Structural highlights

6s24 is a 2 chain structure with sequence from Homo sapiens and Taeniopygia guttata. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.12Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GALT3_TAEGU 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 (PubMed:31932717). Glycosylates FGF23 (PubMed:31932717).^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Molecular basis for fibroblast growth factor 23 O-glycosylation by GalNAc-T3. Nat Chem Biol. 2020 Jan 13. pii: 10.1038/s41589-019-0444-x. doi:, 10.1038/s41589-019-0444-x. PMID:31932717 doi:http://dx.doi.org/10.1038/s41589-019-0444-x
↑ 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. Molecular basis for fibroblast growth factor 23 O-glycosylation by GalNAc-T3. Nat Chem Biol. 2020 Jan 13. pii: 10.1038/s41589-019-0444-x. doi:, 10.1038/s41589-019-0444-x. PMID:31932717 doi:http://dx.doi.org/10.1038/s41589-019-0444-x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6s24"

@@ Line 3: / Line 3: @@
 <StructureSection load='6s24' size='340' side='right'caption='[[6s24]], [[Resolution|resolution]] 2.12&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[6s24]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Taeniopygia_guttata Taeniopygia 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 [https://proteopedia.org/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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.12&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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'>[https://proteopedia.org/fgij/fg.htm?mol=6s24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s24 OCA], [https://pdbe.org/6s24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s24 RCSB], [https://www.ebi.ac.uk/pdbsum/6s24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s24 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/GALT3_TAEGU GALT3_TAEGU] 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 (PubMed:31932717). Glycosylates FGF23 (PubMed:31932717).<ref>PMID:31932717</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Poephila guttata]]
+[[Category: Taeniopygia guttata]]
-[[Category: Bernado, P]]
+[[Category: Bernado P]]
-[[Category: Ceballos-Laita, L]]
+[[Category: Ceballos-Laita L]]
-[[Category: Clausen, H]]
+[[Category: Clausen H]]
-[[Category: Coelho, H]]
+[[Category: Coelho H]]
-[[Category: Companon, I]]
+[[Category: Companon I]]
-[[Category: Corzana, F]]
+[[Category: Corzana F]]
-[[Category: Daniel, E J.P]]
+[[Category: Daniel EJP]]
-[[Category: Gerken, T A]]
+[[Category: Gerken TA]]
-[[Category: Hansen, L]]
+[[Category: Hansen L]]
-[[Category: Hermosilla, P]]
+[[Category: Hermosilla P]]
-[[Category: Hurtado-Guerrero, R]]
+[[Category: Hurtado-Guerrero R]]
-[[Category: Kato, K]]
+[[Category: Kato K]]
-[[Category: Lostao, A]]
+[[Category: Lostao A]]
-[[Category: Marcelo, F]]
+[[Category: Marcelo F]]
-[[Category: Narimatsu, Y]]
+[[Category: Narimatsu Y]]
-[[Category: Rivas, M de las]]
+[[Category: Thureau A]]
-[[Category: Thureau, A]]
+[[Category: De las Rivas M]]
-[[Category: Enzyme kinetic]]
-[[Category: Fgf23]]
-[[Category: Galnac-t]]
-[[Category: Galnac-t3]]
-[[Category: Long-range glycosylation preference]]
-[[Category: Molecular dynamic]]
-[[Category: Phosphate homeostasis]]
-[[Category: Specificity]]
-[[Category: Transferase]]

6s24

From Proteopedia

Current revision

Crystal structure of the TgGalNAc-T3 in complex with UDP, manganese and the peptide 3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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