5kxq

From Proteopedia

(Difference between revisions)

Revision as of 08:12, 8 January 2020

mouse POFUT1 in complex with GDP

Structural highlights

5kxq is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5kxh, 5ky0, 5ky2, 5ky3, 5ky4, 5ky5, 5ky7, 5ky8, 5ky9
Gene:	Pofut1 (LK3 transgenic mice)
Activity:	Peptide-O-fucosyltransferase, with EC number 2.4.1.221
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[OFUT1_MOUSE] Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).^[1] ^[2]

Publication Abstract from PubMed

Protein O-fucosyltransferase 1 (POFUT1) fucosylates the epidermal growth factor (EGF)-like domains found in cell-surface and secreted glycoproteins including Notch and its ligands. Although Notch fucosylation is critical for development, and POFUT1 deficiency leads to human disease, how this enzyme binds and catalyzes the fucosylation of its diverse EGF-like domain substrates has not been determined. Reported here is the X-ray crystal structure of mouse POFUT1 in complex with several EGF-like domains, including EGF12 and EGF26 of Notch. Overall shape complementarity, interactions with invariant atoms of the fucosylation motif and flexible segments on POFUT1 all define its EGF-like-domain binding properties. Using large-scale structural and sequence analysis, we also show that POFUT1 binds EGF-like domains of the hEGF type and that the highly correlated presence of POFUT1 and fucosylatable hEGFs has accompanied animal evolution.

Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1.,Li Z, Han K, Pak JE, Satkunarajah M, Zhou D, Rini JM Nat Chem Biol. 2017 Jul;13(7):757-763. doi: 10.1038/nchembio.2381. Epub 2017 May , 22. PMID:28530709^[3]

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

References

↑ Shi S, Stanley P. Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5234-9. Epub 2003 Apr 15. PMID:12697902 doi:http://dx.doi.org/10.1073/pnas.0831126100
↑ Kim ML, Chandrasekharan K, Glass M, Shi S, Stahl MC, Kaspar B, Stanley P, Martin PT. O-fucosylation of muscle agrin determines its ability to cluster acetylcholine receptors. Mol Cell Neurosci. 2008 Nov;39(3):452-64. doi: 10.1016/j.mcn.2008.07.026. Epub, 2008 Aug 15. PMID:18775496 doi:http://dx.doi.org/10.1016/j.mcn.2008.07.026
↑ Li Z, Han K, Pak JE, Satkunarajah M, Zhou D, Rini JM. Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1. Nat Chem Biol. 2017 Jul;13(7):757-763. doi: 10.1038/nchembio.2381. Epub 2017 May , 22. PMID:28530709 doi:http://dx.doi.org/10.1038/nchembio.2381

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/5kxq"

@@ Line 1: / Line 1: @@
 ==mouse POFUT1 in complex with GDP==
-<StructureSection load='5kxq' size='340' side='right' caption='[[5kxq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='5kxq' size='340' side='right'caption='[[5kxq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5kxq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KXQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5kxq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KXQ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kxh|5kxh]], [[5ky0|5ky0]], [[5ky2|5ky2]], [[5ky3|5ky3]], [[5ky4|5ky4]], [[5ky5|5ky5]], [[5ky7|5ky7]], [[5ky8|5ky8]], [[5ky9|5ky9]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pofut1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptide-O-fucosyltransferase Peptide-O-fucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.221 2.4.1.221] </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=5kxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kxq OCA], [http://pdbe.org/5kxq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kxq RCSB], [http://www.ebi.ac.uk/pdbsum/5kxq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kxq ProSAT]</span></td></tr>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Peptide-O-fucosyltransferase]]
 [[Category: Li, Z]]

5kxq

From Proteopedia

Revision as of 08:12, 8 January 2020

mouse POFUT1 in complex with GDP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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