title: In silico study on the substrate binding manner in human myo-inositol monophosphatase 2.
abstract: The human IMPA2 gene encoding myo-inositol monophosphatase 2 is highly implicated with bipolar disorder but the substrates and the reaction mechanism of myo-inositol monophosphatase 2 have not been well elucidated.9 In the present study, we constructed 3D models of three- and two-Mg(2+)-ion bound myo-inositol monophosphatase 2, and studied substrate-binding manners using the docking program AutoDock3. The subsequent study showed that the three-metal-ion model could interact with myo-inositol monophosphates, as follows: The phosphate moiety coordinated three Mg(2+) ions, and the inositol ring formed hydrogen bonds with the amino acids conserved in the family. Furthermore, the OH group vicinal to the phosphate group formed a hydrogen bond with a non-bridging oxygen atom of the phosphate. These interactions have been proposed as crucial for forming the transitional state, bipyramidal structure in the bovine myo-inositol monophosphatase. We therefore propose that the human myo-inositol monophosphatase 2 interacts with myo-inositol monophosphates in the three-metal-ion bound form, and proceeds the dephosphorylation through the three-metal-ion theory.
authors.affiliation: Department of Bioinformatics, College of Information Science and Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Fujita
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Shujiro
authors.initials: S
authors.lastname: Okuda
authors.forename: Ryo
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuno
authors.forename: Daisuke
authors.initials: D
authors.lastname: Furuta
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Norihisa
authors.initials: N
authors.lastname: Fujita
mesh_terms: D006801:Humans; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008670:Metals / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D007477:Ions; D008670:Metals; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase