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'''HUMAN INOSITOL (1,4,5)-TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/ADP/INS(1,3,4,5)P4''' | '''HUMAN INOSITOL (1,4,5)-TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/ADP/INS(1,3,4,5)P4''' | ||
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[[Category: Schell, M J.]] | [[Category: Schell, M J.]] | ||
[[Category: Williams, R L.]] | [[Category: Williams, R L.]] | ||
[[Category: | [[Category: Adp]] | ||
[[Category: | [[Category: Inositol phosphate kinase]] | ||
[[Category: | [[Category: Ip4]] | ||
[[Category: | [[Category: Transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:03:24 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 10:03, 3 May 2008
HUMAN INOSITOL (1,4,5)-TRISPHOSPHATE 3-KINASE COMPLEXED WITH MN2+/ADP/INS(1,3,4,5)P4
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
1W2D is a Single protein structure of sequence from Homo sapiens. 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 Page seeded by OCA on Sat May 3 13:03:24 2008
