1w2c

From Proteopedia

Revision as of 15:17, 5 November 2007

HUMAN INOSITOL (1,4,5) TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/AMPPNP/INS(1,4,5)P3

Overview

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.

About this Structure

1W2C is a Single protein structure of sequence from Homo sapiens with MN, SO4, ANP and I3P as ligands. Active as Transferase, with EC number 2.1.7.127 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase., Gonzalez B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, Williams RL, Mol Cell. 2004 Sep 10;15(5):689-701. PMID:15350214

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