View source for 7a17


==Crystal structure of the 5-phosphatase domain of Synaptojanin1 bound to its substrate diC8-PI(3,4,5)P3 in complex with a nanobody==
<StructureSection load='7a17' size='340' side='right'caption='[[7a17]], [[Resolution|resolution]] 2.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7a17]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A17 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.73&#8491;</td></tr>
<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=IP9:(2R)-3-{[(R)-{[(1S,2S,3R,4S,5S,6S)-2,6-DIHYDROXY-3,4,5-TRIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}(HYDROXY)PHOSPHORYL]OXY}PROPANE-1,2-DIYL+DIOCTANOATE'>IP9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7a17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a17 OCA], [https://pdbe.org/7a17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a17 RCSB], [https://www.ebi.ac.uk/pdbsum/7a17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a17 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SYNJ1_HUMAN SYNJ1_HUMAN] Inositol 5-phosphatase which has a role in clathrin-mediated endocytosis.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Synaptojanin1 (Synj1) is a phosphoinositide phosphatase, important in clathrin uncoating during endocytosis of presynaptic vesicles. It was identified as a potential drug target for Alzheimer's disease, Down syndrome, and TBC1D24-associated epilepsy, while also loss-of-function mutations in Synj1 are associated with epilepsy and Parkinson's disease. Despite its involvement in a range of disorders, structural, and detailed mechanistic information regarding the enzyme is lacking. Here, we report the crystal structure of the 5-phosphatase domain of Synj1. Moreover, we also present a structure of this domain bound to the substrate diC8-PI(3,4,5)P(3), providing the first image of a 5-phosphatase with a trapped substrate in its active site. Together with an analysis of the contribution of the different inositide phosphate groups to catalysis, these structures provide new insights in the Synj1 mechanism. Finally, we analysed the effect of three clinical missense mutations (Y793C, R800C, Y849C) on catalysis, unveiling the molecular mechanisms underlying Synj1-associated disease.

A structure of substrate-bound Synaptojanin1 provides new insights in its mechanism and the effect of disease mutations.,Paesmans J, Martin E, Deckers B, Berghmans M, Sethi R, Loeys Y, Pardon E, Steyaert J, Verstreken P, Galicia C, Versees W Elife. 2020 Dec 22;9:e64922. doi: 10.7554/eLife.64922. PMID:33349335<ref>PMID:33349335</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7a17" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Galicia C]]
[[Category: Martin E]]
[[Category: Paesmans J]]
[[Category: Versees W]]