Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

inositol-phosphate phosphatase By Reference

Mammalian brain inositol monophosphatase (IMPase) provides inositol for the biosynthesis of the key secondary messenger precursor, phosphatidylinositol 4,5-bisphosphate. Phosphatidylinositol 4,5-bisphosphate is hydrolysed by phosphatidylinositidase C in response to receptor occupation to give diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (Ins 1,4,5-P3), both of which mediate signal transduction through specific interactions with their own targets. DAG activates protein kinase C which modulates the activity of many enzymes through phosphorylation, while Ins 1,4,5-P3 causes the release of calcium ions from an intracellular store. Brain cells vary in their ability to take up inositol and a series of phosphatases exist to sequentially hydrolyse Ins 1,4,5-P3 and other inositol polyphosphates via the bisphosphates to give inositol 1- and 4-monophosphates, substrates for IMPase. The effect of blocking IMPase with inhibitor Li+ cations is depletion of free inositol in brain cells and, thus, several groups have suggested that IMPase might be the target for the lithium ions in manic depression therapy.




• Summary
• Step 1
• Step 2
• Step 3
• Products

Two Mg(II) ions bind to the enzyme. A water bound to Mg(II), aided by the phosphoryl group of the reactant forms an attacking nucleophilic hydroxide ion to cleave the phosphate-inositolate bond. Subsequent proton transfer steps occur to eliminate the products, myo-inositol and an inorganic phosphate enabling the active site to be ready for another round of catalysis. It has been observed Lithium is a powerful inhibitor of the enzyme due to binding to where one of the magnesium ions usually is found, preventing the phosphate group from leaving.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Ile	P29218	92	1ima	92
Asp	P29218	90	1ima	90
Asp	P29218	220	1ima	220
Asp	P29218	93	1ima	93
Glu	P29218	70	1ima	70
Thr	P29218	95	1ima	95

Step Components

overall reactant used, proton transfer, overall product formed, intermediate formation, bimolecular nucleophilic substitution, intermediate terminated, native state of enzyme regenerated, proton relay, dephosphorylation, intermediate collapse



Step 1.

The phosphoryl oxygen on the myo-inositol phosphate is protonated by a water molecule. This activates the water to then nucleophilically attack the phosphorous atom causing the phosphate bond to break. It is thought that proton transfer and the Sn2 reaction occur simultaneously.



Step 2.

A phosphoryl hydroxide ion donates a proton to Glu70. The magnesium ion stabilises the oxyanion negative charge.



Step 3.

Glu70 rotates and protonates the oxyanion intermediate via a water molecule to form the final product, myo-inositol. The water molecule maintains its coordination with a magnesium ion.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• The Genetic Background of Abnormalities in Metabolic Pathways of Phosphoinositides and Their Linkage with the Myotubular Myopathies, Neurodegenerative Disorders, and Carcinogenesis.
• Novel insights into D-Pinitol based therapies: a link between tau hyperphosphorylation and insulin resistance.
• Activities, substrate specificity, and genetic interactions of fission yeast Siw14, a cysteinyl-phosphatase-type inositol pyrophosphatase.
• OsIPK2, a Rice Inositol Polyphosphate Kinase Gene, Is Involved in Phosphate Homeostasis and Root Development.
• Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2
• Valproate regulates inositol synthesis by reducing expression of myo-inositol-3-phosphate synthase.
• Multiple Inositol Polyphosphate Phosphatase Compartmentalization Separates Inositol Phosphate Metabolism from Inositol Lipid Signaling.
• Role of inositol polyphosphate-4-phosphatase type II in oncogenesis of digestive system tumors.
• RhoB promotes Salmonella survival by regulating autophagy.
• Interaction of calcium responsive proteins and transcriptional factors with the PHO regulon in yeasts and fungi.
• Microbial Phytases: Properties and Applications in the Food Industry.