2czi: Difference between revisions

Revision as of 23:24, 3 May 2008

Crystal structure of human myo-inositol monophosphatase 2 (IMPA2) with calcium and phosphate ions

OverviewOverview

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.

About this StructureAbout this Structure

2CZI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sat May 3 23:24:28 2008

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OCA

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 [[Image:2czi.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2czi", creates the "Structure Box" on the page.
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-|ACTIVITY= <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>
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-|GENE= IMPA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
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-|RELATEDENTRY=[[2czh|2CZH]], [[2czk|2CZK]], [[2ddk|2DDK]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2czi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2czi OCA], [http://www.ebi.ac.uk/pdbsum/2czi PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2czi RCSB]</span>
-}}
 '''Crystal structure of human myo-inositol monophosphatase 2 (IMPA2) with calcium and phosphate ions'''
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 [[Category: Yokoyama, S.]]
 [[Category: Yoshikawa, T.]]
-[[Category: bipolar disorder]]
+[[Category: Bipolar disorder]]
-[[Category: myo-inositol monophosphatase (impa)]]
+[[Category: National project on protein structural and functional analyse]]
-[[Category: national project on protein structural and functional analyse]]
+[[Category: Nppsfa]]
-[[Category: nppsfa]]
+[[Category: Riken structural genomics/proteomics initiative]]
-[[Category: riken structural genomics/proteomics initiative]]
+[[Category: Rsgi]]
-[[Category: rsgi]]
+[[Category: Structural genomic]]
-[[Category: structural genomic]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 23:24:28 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:28:21 2008''