1W2F

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

Summary for 1W2F

• Entry DOI: 10.2210/pdb1w2f/pdb
• Related: 1W2C 1W2D
• Descriptor: INOSITOL-TRISPHOSPHATE 3-KINASE A, SULFATE ION (3 entities in total)
• Functional Keywords: inositol phosphate kinase, transferase, calmodulin-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 64136.97

Authors

Gonzalez, B.,Schell, M.J.,Irvine, R.F.,Williams, R.L. (deposition date: 2004-07-01, release date: 2004-09-09, Last modification date: 2024-10-16)

Primary citation

Gonzalez, B.,Schell, M.J.,Letcher, A.J.,Veprintsev, D.B.,Irvine, R.F.,Williams, R.L.
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-, 2004

PubMed 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.

PubMed: 15350214
DOI: 10.1016/J.MOLCEL.2004.08.004

Experimental method

X-RAY DIFFRACTION (1.8 Å)