PDBsum entry 2czi

Hydrolase

PDB id: 2czi

Contents

Protein chain

259 a.a. *

Ligands

PO4

Metals

_CA ×2

Waters ×7

* Residue conservation analysis

PDB id:

2czi

Name:

Hydrolase

Title:

Crystal structure of human myo-inositol monophosphatase 2 (impa2) with calcium and phosphate ions

Structure:

Inositol monophosphatase 2. Chain: a. Synonym: impase 2, imp 2, inositol-1(or 4)-monophosphatase 2, myo- inositol monophosphatase a2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: impa2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

3.00Å R-factor: 0.250 R-free: 0.286

Authors:

R.Arai,K.Ito,T.Ohnishi,H.Ohba,T.Yoshikawa,M.Shirouzu,S.Yokoyama,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

R.Arai et al. (2007). Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures. Proteins, 67, 732-742. PubMed id: 17340635 DOI: 10.1002/prot.21299

Date:

13-Jul-05 Release date: 25-Jul-06

Protein chain

O14732  (IMPA2_HUMAN) -  Inositol monophosphatase 2 from Homo sapiens

Seq: 288 a.a.

Struc: 259 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.3.25 - inositol-phosphate phosphatase.
• Pathway: myo-Inositol Biosynthesis
• Reaction: a myo-inositol phosphate + H2O = myo-inositol + phosphate

myo-inositol phosphate + H2O = myo-inositol + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1002/prot.21299

Proteins 67:732-742 (2007)

PubMed id: 17340635

Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures.

R.Arai, K.Ito, T.Ohnishi, H.Ohba, R.Akasaka, Y.Bessho, K.Hanawa-Suetsugu, T.Yoshikawa, M.Shirouzu, S.Yokoyama.

ABSTRACT

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.

Selected figure(s)

Figure 4.
Figure 4. The structure of the active site region of human IMPA2. (A) The structure of the active site region of IMPA2 Crystal 1 and the composite annealed omit electron density map contoured at 1 (2.7 Å resolution) (stereoview). (B) The structure of the active site region of IMPA2 Crystal 2. (C) The structure of the active site region of IMPA2 Crystal 3. (D) The structure of the active site region of IMPA2 Crystal 4 (stereoview). Two calcium ions and one phosphate ion are superimposed with the F[o] - F[c] electron density map contoured at 3 (3.0 Å resolution).

Figure 6.
Figure 6. The sites of the three nonsynonymous polymorphisms (His76Tyr, Arg148Gln, and Ala181Val) reported in IMPA2 on the IMPA2 dimer (Crystal 1).

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2007, 67, 732-742) copyright 2007.

Figures were selected by an automated process.