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| ==Structure of human inositol monophosphatase 1== | | ==Structure of human inositol monophosphatase 1== |
- | <StructureSection load='4as4' size='340' side='right' caption='[[4as4]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4as4' size='340' side='right'caption='[[4as4]], [[Resolution|resolution]] 1.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4as4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AS4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4as4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AS4 FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.7Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1awb|1awb]], [[1ima|1ima]], [[1imb|1imb]], [[1imc|1imc]], [[1imd|1imd]], [[1ime|1ime]], [[1imf|1imf]], [[2hhm|2hhm]], [[4as5|4as5]]</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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-phosphate_phosphatase Inositol-phosphate phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.25 3.1.3.25] </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=4as4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as4 OCA], [https://pdbe.org/4as4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4as4 RCSB], [https://www.ebi.ac.uk/pdbsum/4as4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4as4 ProSAT]</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=4as4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4as4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4as4 RCSB], [http://www.ebi.ac.uk/pdbsum/4as4 PDBsum]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/IMPA1_HUMAN IMPA1_HUMAN]] Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates.<ref>PMID:17068342</ref> | + | [https://www.uniprot.org/uniprot/IMPA1_HUMAN IMPA1_HUMAN] Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates.<ref>PMID:17068342</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| </div> | | </div> |
| + | <div class="pdbe-citations 4as4" style="background-color:#fffaf0;"></div> |
| | | |
| ==See Also== | | ==See Also== |
- | *[[Inositol Monophosphatase|Inositol Monophosphatase]] | + | *[[Inositol monophosphatase 3D structures|Inositol monophosphatase 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Inositol-phosphate phosphatase]] | + | [[Category: Large Structures]] |
- | [[Category: Churchill, G C]] | + | [[Category: Churchill GC]] |
- | [[Category: Halliday, A C]] | + | [[Category: Halliday AC]] |
- | [[Category: Knight, M]] | + | [[Category: Knight M]] |
- | [[Category: Lack, N A]] | + | [[Category: Lack NA]] |
- | [[Category: Lowe, E D]] | + | [[Category: Lowe ED]] |
- | [[Category: Singh, N]] | + | [[Category: Singh N]] |
- | [[Category: Bipolar disorder]]
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- | [[Category: Hydrolase]]
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- | [[Category: Lithium]]
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| Structural highlights
Function
IMPA1_HUMAN Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates.[1]
Publication Abstract from PubMed
Inositol monophosphatase (IMPase) catalyses the hydrolysis of inositol monophosphate to inositol and is crucial in the phosphatidylinositol (PI) signalling pathway. Lithium, which is the drug of choice for bipolar disorder, inhibits IMPase at therapeutically relevant plasma concentrations. Both mouse IMPase 1 (MmIMPase 1) and human IMPase 1 (HsIMPase 1) were cloned into pRSET5a, expressed in Escherichia coli, purified and crystallized using the sitting-drop method. The structures were solved at resolutions of 2.4 and 1.7 A, respectively. Comparison of MmIMPase 1 and HsIMPase 1 revealed a core r.m.s. deviation of 0.516 A.
Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens.,Singh N, Halliday AC, Knight M, Lack NA, Lowe E, Churchill GC Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Oct 1;68(Pt 10):1149-52., doi: 10.1107/S1744309112035191. Epub 2012 Sep 22. PMID:23027737[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T. Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1. J Biol Chem. 2007 Jan 5;282(1):637-46. Epub 2006 Oct 26. PMID:17068342 doi:http://dx.doi.org/10.1074/jbc.M604474200
- ↑ Singh N, Halliday AC, Knight M, Lack NA, Lowe E, Churchill GC. Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Oct 1;68(Pt 10):1149-52., doi: 10.1107/S1744309112035191. Epub 2012 Sep 22. PMID:23027737 doi:http://dx.doi.org/10.1107/S1744309112035191
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