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| | ==Crystal structure of human myo-inositol monophosphatase 2 (IMPA2) (orthorhombic form)== | | ==Crystal structure of human myo-inositol monophosphatase 2 (IMPA2) (orthorhombic form)== |
| - | <StructureSection load='2ddk' size='340' side='right' caption='[[2ddk]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='2ddk' size='340' side='right'caption='[[2ddk]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ddk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DDK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ddk]] 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=2DDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DDK FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2czh|2czh]], [[2czi|2czi]], [[2czk|2czk]]</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]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IMPA2, IMP.18P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2ddk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ddk OCA], [https://pdbe.org/2ddk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ddk RCSB], [https://www.ebi.ac.uk/pdbsum/2ddk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ddk ProSAT], [https://www.topsan.org/Proteins/RSGI/2ddk TOPSAN]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ddk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ddk OCA], [http://pdbe.org/2ddk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ddk RCSB], [http://www.ebi.ac.uk/pdbsum/2ddk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ddk ProSAT], [http://www.topsan.org/Proteins/RSGI/2ddk TOPSAN]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IMPA2_HUMAN IMPA2_HUMAN]] Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li(+) action in brain.<ref>PMID:17068342</ref> | + | [https://www.uniprot.org/uniprot/IMPA2_HUMAN IMPA2_HUMAN] Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li(+) action in brain.<ref>PMID:17068342</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Inositol Monophosphatase|Inositol Monophosphatase]] | + | *[[Inositol monophosphatase 3D structures|Inositol monophosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Inositol-phosphate phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Arai, R]] | + | [[Category: Arai R]] |
| - | [[Category: Bessho, Y]] | + | [[Category: Bessho Y]] |
| - | [[Category: Ito, K]] | + | [[Category: Ito K]] |
| - | [[Category: Kamo-Uchikubo, T]] | + | [[Category: Kamo-Uchikubo T]] |
| - | [[Category: Ohba, H]] | + | [[Category: Ohba H]] |
| - | [[Category: Ohnishi, T]] | + | [[Category: Ohnishi T]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Shirouzu M]] |
| - | [[Category: Shirouzu, M]] | + | [[Category: Yokoyama S]] |
| - | [[Category: Yokoyama, S]] | + | [[Category: Yoshikawa T]] |
| - | [[Category: Yoshikawa, T]] | + | |
| - | [[Category: Bipolar disorder]]
| + | |
| - | [[Category: Febrile seizure]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Rsgi]]
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| - | [[Category: Schizophrenia]]
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| Structural highlights
Function
IMPA2_HUMAN Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li(+) action in brain.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The human IMPA2 gene, which encodes myo-inositol monophosphatase 2 (IMPA2), is mapped onto 18p11.2, a susceptibility region for bipolar disorder. This chromosomal region has also been proposed to include a susceptibility locus for schizophrenia and febrile seizures. Here we report the crystal structures of human IMPA2 and its complex with calcium and phosphate ions. Human IMPA2 comprises an alpha-beta protein with a five-layered sandwich of alpha-helices and beta-sheets (alpha-beta-alpha-beta-alpha). The crystal structure and analytical ultracentrifugation results indicated that IMPA2 exists as a dimer in solution. The overall structure of IMPA2 is similar to that of IMPA1, except for the loop regions. In IMPA1, the loop region (31-43) is located at the entrance of the active site cavity. In the corresponding region (42-54) of IMPA2, the residues are disordered and partially form an alpha-helix. The structural difference in the opening of the active site cavity suggests that the substrate specificity differs between IMPA1 and IMPA2. The widely opened cavity of IMPA2 implies that the physiological substrate may be a larger compound than inositol monophosphate. The structure of IMPA2 complexed with Ca2+ revealed two metals and one phosphate binding sites, which were the same sites as in IMPA1 complexed with Mn2+ and phosphate, suggesting that the mechanism of the enzymatic reaction is similar to that of IMPA1. The crystal structures of human IMPA2 are useful for understanding the effect of nonsynonymous polymorphism reported in IMPA2, and will contribute to further functional analyses of IMPA2 that potentially predisposes to the vulnerabilities of bipolar disorder, schizophrenia, and febrile seizures.
Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures.,Arai R, Ito K, Ohnishi T, Ohba H, Akasaka R, Bessho Y, Hanawa-Suetsugu K, Yoshikawa T, Shirouzu M, Yokoyama S Proteins. 2007 May 15;67(3):732-42. PMID:17340635[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
- ↑ Arai R, Ito K, Ohnishi T, Ohba H, Akasaka R, Bessho Y, Hanawa-Suetsugu K, Yoshikawa T, Shirouzu M, Yokoyama S. Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures. Proteins. 2007 May 15;67(3):732-42. PMID:17340635 doi:10.1002/prot.21299
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