5f86
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==Crystal structure of Drosophila Poglut1 (Rumi) complexed with its substrate protein (EGF repeat)== | ==Crystal structure of Drosophila Poglut1 (Rumi) complexed with its substrate protein (EGF repeat)== | ||
| - | <StructureSection load='5f86' size='340' side='right' caption='[[5f86]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5f86' size='340' side='right'caption='[[5f86]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5f86]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F86 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5f86]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F86 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F86 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5f86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f86 OCA], [https://pdbe.org/5f86 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f86 RCSB], [https://www.ebi.ac.uk/pdbsum/5f86 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f86 ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[http://omim.org/entry/306900 306900]]; also known as Christmas disease.<ref>PMID:8295821</ref> <ref>PMID:2592373</ref> <ref>PMID:2743975</ref> <ref>PMID:6603618</ref> <ref>PMID:3009023</ref> <ref>PMID:3790720</ref> <ref>PMID:3401602</ref> <ref>PMID:3243764</ref> <ref>PMID:2713493</ref> <ref>PMID:2714791</ref> <ref>PMID:2773937</ref> <ref>PMID:2775660</ref> <ref>PMID:2753873</ref> <ref>PMID:2738071</ref> <ref>PMID:2472424</ref> <ref>PMID:2339358</ref> <ref>PMID:2372509</ref> <ref>PMID:2162822</ref> <ref>PMID:1958666</ref> <ref>PMID:1902289</ref> <ref>PMID:1346975</ref> <ref>PMID:1615485</ref> <ref>PMID:8257988</ref> <ref>PMID:8076946</ref> <ref>PMID:8199596</ref> <ref>PMID:7981722</ref> <ref>PMID:8680410</ref> <ref>PMID:9222764</ref> <ref>PMID:9590153</ref> <ref>PMID:9452115</ref> <ref>PMID:9600455</ref> <ref>PMID:10698280</ref> <ref>PMID:10094553</ref> <ref>PMID:11122099</ref> <ref>PMID:12588353</ref> <ref>PMID:12604421</ref> Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide. Defects in F9 are the cause of thrombophilia due to factor IX defect (THPH8) [MIM:[http://omim.org/entry/300807 300807]]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/RUMI_DROME RUMI_DROME] Protein O-glucosyltransferase. Catalyzes the reaction that attaches glucose through an O-glycosidic linkage to a conserved serine residue in epidermal growth factor-like repeats. Regulates Notch signaling by glucosylating Notch in the ER, glucosylation is required for the correct folding and cleavage of Notch.<ref>PMID:18243100</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Rumi O-glucosylates the EGF repeats of a growing list of proteins essential in metazoan development, including Notch. Rumi is essential for Notch signaling, and Rumi dysregulation is linked to several human diseases. Despite Rumi's critical roles, it is unknown how Rumi glucosylates a serine of many but not all EGF repeats. Here we report crystal structures of Drosophila Rumi as binary and ternary complexes with a folded EGF repeat and/or donor substrates. These structures provide insights into the catalytic mechanism and show that Rumi recognizes structural signatures of the EGF motif, the U-shaped consensus sequence, C-X-S-X-(P/A)-C and a conserved hydrophobic region. We found that five Rumi mutations identified in cancers and Dowling-Degos disease are clustered around the enzyme active site and adversely affect its activity. Our study suggests that loss of Rumi activity may underlie these diseases, and the mechanistic insights may facilitate the development of modulators of Notch signaling. | ||
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| + | Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations.,Yu H, Takeuchi H, Takeuchi M, Liu Q, Kantharia J, Haltiwanger RS, Li H Nat Chem Biol. 2016 Sep;12(9):735-40. doi: 10.1038/nchembio.2135. Epub 2016 Jul, 18. PMID:27428513<ref>PMID:27428513</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5f86" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Factor IX 3D structures|Factor IX 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Li HL]] |
| - | [[Category: | + | [[Category: Yu HJ]] |
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Current revision
Crystal structure of Drosophila Poglut1 (Rumi) complexed with its substrate protein (EGF repeat)
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