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| | <StructureSection load='6wro' size='340' side='right'caption='[[6wro]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='6wro' size='340' side='right'caption='[[6wro]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6wro]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WRO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WRO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wro]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WRO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WRO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">INPP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Inositol-1,4-bisphosphate_1-phosphatase Inositol-1,4-bisphosphate 1-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.57 3.1.3.57] </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=6wro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wro OCA], [https://pdbe.org/6wro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wro RCSB], [https://www.ebi.ac.uk/pdbsum/6wro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wro ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wro OCA], [http://pdbe.org/6wro PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wro RCSB], [http://www.ebi.ac.uk/pdbsum/6wro PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wro ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/INPP_BOVIN INPP_BOVIN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Inositol-1,4-bisphosphate 1-phosphatase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dollins, D E]] | + | [[Category: Dollins DE]] |
| - | [[Category: Endo-Streeter, S]] | + | [[Category: Endo-Streeter S]] |
| - | [[Category: York, J D]] | + | [[Category: York JD]] |
| - | [[Category: Bipolar disorder]]
| + | |
| - | [[Category: Cellular signaling]]
| + | |
| - | [[Category: Inositol phosphate]]
| + | |
| - | [[Category: Manic depressive illness]]
| + | |
| - | [[Category: Metal binding]]
| + | |
| - | [[Category: Neurological disease]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
INPP_BOVIN
Publication Abstract from PubMed
Inositol polyphosphate 1-phosphatase (INPP1) is a prototype member of metal-dependent/lithium-inhibited phosphomonoesterase protein family defined by a conserved three-dimensional core structure. Enzymes within this family function in distinct pathways including: inositide signaling, gluconeogenesis, and sulfur assimilation. Using structural and biochemical studies, we report the effect of substrate and lithium on a network of metal binding sites within the catalytic center of INPP1. We find that lithium preferentially occupies a key site involved in metal-activation only when substrate or product is added. Mutation of a conserved residue that selectively coordinates the putative lithium-binding site results in a dramatic 100-fold reduction in the inhibitory constant as compared to wild-type. Furthermore, we report the INPP1/inositol 1,4-bisphosphate complex which illuminates key features of the enzyme active site. Our results provide insights into a structural basis for uncompetitive lithium inhibition, substrate recognition and define a sequence motif for metal binding within this family of regulatory phosphatases.
A Structural Basis for Lithium and Substrate Binding of an Inositide Phosphatase.,Dollins DE, Xiong JP, Endo-Streeter S, Anderson DE, Bansal VS, Ponder JW, Ren Y, York JD J Biol Chem. 2020 Nov 10. pii: RA120.014057. doi: 10.1074/jbc.RA120.014057. PMID:33172890[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dollins DE, Xiong JP, Endo-Streeter S, Anderson DE, Bansal VS, Ponder JW, Ren Y, York JD. A Structural Basis for Lithium and Substrate Binding of an Inositide Phosphatase. J Biol Chem. 2020 Nov 10. pii: RA120.014057. doi: 10.1074/jbc.RA120.014057. PMID:33172890 doi:http://dx.doi.org/10.1074/jbc.RA120.014057
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