Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

inositol-1,4-bisphosphate 1-phosphatase By Reference

Inositol polyphosphate 1 -phosphatase (l-ptase) removes the l-position phosphate from inositol 1,4-bisphosphate, yielding inositol 4-phosphate. l-Ptase is a ubiquitous monomeric enzyme that requires Mg2+ for activity and is potently inhibited by Li+, leading to its use in therapeutic targets of lithium treatment for manic-depressive illnesses.




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

As with most phosphatases the mechanism involves nucleophilic attack on the phosphate group. The nucleophile is an activated water molecule, which is co-ordinated to two magnesium cofactors and then activated by Thr158. This attacks the phosphate group forming a trigonal bipyramidal intermediate which is stabilised by the magnesium ions, break down of this leads to the the inositol 4-phosphate.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Glu	P21327	79	1inp	79
Asp	P21327	54	1inp	54
Asp	P21327	153	1inp	153
Asp	P21327	156	1inp	156
Asp	P21327	317	1inp	317
Ile	P21327	155	1inp	155
Thr	P21327	158	1inp	158

Step Components

overall reactant used, proton transfer, overall product formed, unimolecular elimination by the conjugate base, bimolecular nucleophilic addition, native state of enzyme regenerated, inferred reaction step, proton relay



Step 1.

The Asp54/Thr158 network deprotonates a water molecule activating it for nucleophilic attack on the phosphate. The penta-covalent intermediate formed is stabilized by the magnesium ions.



Step 2.

The intermediate collapses yielding inositol 4-phosphate.



Step 3.

Inferred step- product is protonated and the enzyme is regenerated in its native state.



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.
• Commentary on: The actin bundling activity of ITPKA mainly accounts for its migration-promoting effect in lung cancer cells.
• Activation Mechanisms and Diverse Functions of Mammalian Phospholipase C.
• Myo-D-inositol Trisphosphate Signalling in Oomycetes.
• Low dissolved oxygen supply functions as a global regulator of the growth and metabolism of Aurantiochytrium sp. PKU#Mn16 in the early stages of docosahexaenoic acid fermentation.
• GhIMP10D, an inositol monophosphates family gene, enhances ascorbic acid and antioxidant enzyme activities to confer alkaline tolerance in Gossypium hirsutum L.
• A mutation in Arabidopsis SAL1 alters its in vitro activity against IP₃ and delays developmental leaf senescence in association with lower ROS levels.
• Transcriptomics analyses reveal the effects of Pentagamaboronon-0-ol on PI3K/Akt and cell cycle of HER2+ breast cancer cells.
• Effect of dapagliflozin on proteomics and metabolomics of serum from patients with type 2 diabetes.
• Application of proteomics to determine the mechanism of ozone on sweet cherries (Prunus avium L.) by time-series analysis.
• Phospholipases in Gliomas: Current Knowledge and Future Perspectives from Bench to Bedside.