1-phosphatidylinositol-5-phosphate 4-kinase

 

Type II beta phosphotidylinositol phosphate kinase catalyses the phosphorylation of PI3P or PI5P on the 4-hydroxyl group and therefore it plays a central role in signal transduction. It has been shown to interact with its alpha isoform to enhance its enzymatic activity.

 

Reference Protein and Structure

Sequence
P78356 UniProt (2.7.1.149) IPR023610 (Sequence Homologues) (PDB Homologues)
Biological species
Homo sapiens (Human) Uniprot
PDB
1bo1 - PHOSPHATIDYLINOSITOL PHOSPHATE KINASE TYPE II BETA (3.0 Å) PDBe PDBsum 1bo1
Catalytic CATH Domains
3.30.800.10 CATHdb 3.30.810.10 CATHdb (see all for 1bo1)
Cofactors
Magnesium(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:2.7.1.149)

ATP(4-)
CHEBI:30616ChEBI
+
1-phosphatidyl-1D-myo-inositol 5-phosphate(3-)
CHEBI:57795ChEBI
→
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate(5-)
CHEBI:58456ChEBI
+
ADP(3-)
CHEBI:456216ChEBI
+
hydron
CHEBI:15378ChEBI
Alternative enzyme names: Type II PIP kinase,

Enzyme Mechanism

Introduction

Asp278 acts as a base to deprotonate the 4-hydroxyl group of inositol ring. The negatively charged oxygen atom of the hydroxyl group acts as a nucleophile and directly attack the terminal-phosphate of ATP. The product is formed via a SN2 mechanism. Mg2+ and Lys150 which coordinates with alpha-phosphate group of ATP stabilise the transition state.

Catalytic Residues Roles

UniProt PDB* (1bo1)
Asp278 Asp278A It acts as a base to deprotonate the 4-hydroxyl group of inositol ring to promote its attack on the terminal phosphate of ATP. proton shuttle (general acid/base)
Lys150 Lys150A It coordinates with alpha-phosphate group of ATP to stabilise the transition state. electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Rao VD et al. (1998), Cell, 94, 829-839. Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation. PMID:9753329.
  2. Bultsma Y et al. (2010), Biochem J, 430, 223-235. PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. DOI:10.1042/BJ20100341. PMID:20583997.
  3. Hanks SK et al. (1995), FASEB J, 9, 576-596. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. PMID:7768349.

Step 1.

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Catalytic Residues Roles

Residue Roles
Asp278A proton shuttle (general acid/base)
Lys150A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Mei Leung, Gemma L. Holliday, Morwenna Hall