PDBsum entry 1w2f

Transferase

PDB id: 1w2f

Contents

Protein chain

276 a.a. *

Ligands

SO4 ×4

Waters ×265

* Residue conservation analysis

PDB id:

1w2f

Name:

Transferase

Title:

Human inositol (1,4,5)-trisphosphate 3-kinase substituted with selenomethionine

Structure:

Inositol-trisphosphate 3-kinase a. Chain: a, b. Fragment: catalytic domain, residues 186-461. Synonym: inositol 1,4,5-trisphosphate 3-kinase, ip3-3k. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: de3.

Resolution:

1.80Å R-factor: 0.204 R-free: 0.241

Authors:

B.Gonzalez,M.J.Schell,R.F.Irvine,R.L.Williams

Key ref:

B.González et al. (2004). Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase. Mol Cell, 15, 689-701. PubMed id: 15350214 DOI: 10.1016/j.molcel.2004.08.004

Date:

01-Jul-04 Release date: 09-Sep-04

Protein chains

P23677  (IP3KA_HUMAN) -  Inositol-trisphosphate 3-kinase A from Homo sapiens

Seq: 461 a.a.

Struc: 276 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.1.127 - inositol-trisphosphate 3-kinase.
• Pathway: myo-Inositol Phosphate Metabolism
• Reaction: 1D-myo-inositol 1,4,5-trisphosphate + ATP = 1D-myo-inositol 1,3,4,5- tetrakisphosphate + ADP + H⁺
• Cofactor: Ca(2+)

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

reference

DOI no: 10.1016/j.molcel.2004.08.004

Mol Cell 15:689-701 (2004)

PubMed id: 15350214

Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase.

B.González, M.J.Schell, A.J.Letcher, D.B.Veprintsev, R.F.Irvine, R.L.Williams.

ABSTRACT

Mammalian cells produce a variety of inositol phosphates (InsPs), including Ins(1,4,5)P3 that serves both as a second messenger and as a substrate for inositol polyphosphate kinases (IPKs), which further phosphorylate it. We report the structure of an IPK, the human Ins(1,4,5)P3 3-kinase-A, both free and in complexes with substrates and products. This enzyme catalyzes transfer of a phosphate from ATP to the 3-OH of Ins(1,4,5)P3, and its X-ray crystal structure provides a template for understanding a broad family of InsP kinases. The catalytic domain consists of three lobes. The N and C lobes bind ATP and resemble protein and lipid kinases, despite insignificant sequence similarity. The third lobe binds inositol phosphate and is a unique four-helix insertion in the C lobe. This lobe embraces all of the phosphates of Ins(1,4,5)P3 in a positively charged pocket, explaining the enzyme's substrate specificity and its inability to phosphorylate PtdIns(4,5)P2, the membrane-resident analog of Ins(1,4,5)P3.

Selected figure(s)

Figure 1.
Figure 1. The Overall Fold of IP[3]-3K Catalytic Domain(A) A ribbon diagram of IP[3]-3K in a complex with Mn^2+/AMPPNP/Ins(1,4,5)P[3]. The N lobe is colored orange, the C lobe yellow, the IP lobe purple, and the hinge green. The conserved IDFG, GSSLL, and DxK motifs are colored pink, cyan, and brown, respectively. This and all other molecular illustrations were prepared with PYMOL.(B) A topology diagram of the catalytic domain. Helix α0[N] is ordered only in the absence of substrates or products. The dashed arrow indicates an additional strand that would be characteristic of the N lobes of PKs.(C) Ribbon diagrams of the catalytic domains of PI3Kγ and PIPKIIβ with N and C lobes colored as in (A).

Figure 3.
Figure 3. Substrate Binding by IP[3]-3K(A) A view of the active site showing the ATP analog and Ins(1,4,5)P[3] bound to the enzyme. The subdomains and motifs are colored as in Figure 1. Side chains interacting with the ligands are shown as sticks and ligand-bound water molecules as white spheres.(B) A schematic of the interactions with the ligands made with LIGPLOT.(C) A surface illustration of the IP[3]-3K catalytic domain colored by electrostatic potential with negatively charged regions red and positive blue. The bound AMPPNP is shown as green sticks and the Ins(1,4,5)P[3] as yellow sticks.(D) A close-up of the ATP binding pocket in the presence of AMPPNP (left) and in its absence (right), showing Trp188 and His194 from the putative auto-inhibitory region mimicking the interactions formed by ATP.

The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 15, 689-701) copyright 2004.

Figures were selected by an automated process.