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

@article{citeulike:220855, 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.}, author = {Gonzalez, B. and Schell, M. J. and Letcher, A. J. and Veprintsev, D. B. and Irvine, R. F. and Williams, R. L.}, citeulike-article-id = {220855}, journal = {Molecular cell}, keywords = {1-phosphatidylinositol, 3-kinase, adenosine, alcohol, amino, catalytic, crystallography, domain, homology, inositol, phosphatidylinositol, phosphorylation, phosphotransferase, protein, specificity, structure, substrate}, number = {5}, pages = {689--701}, posted-at = {2005-06-06 17:47:49}, priority = {2}, title = {Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase}, volume = {15}, year = {2004} }

TY - JOUR ID - citeulike:220855 L3 - citeulike-article-id:220855 N2 - 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. IS - 5 JF - Molecular cell EP - 701 TI - Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase VL - 15 SP - 689 KW - 1-phosphatidylinositol KW - 3-kinase KW - adenosine KW - alcohol KW - amino KW - catalytic KW - crystallography KW - domain KW - homology KW - inositol KW - phosphatidylinositol KW - phosphorylation KW - phosphotransferase KW - protein KW - specificity KW - structure KW - substrate AU - Gonzalez, B AU - Schell, MJ AU - Letcher, AJ AU - Veprintsev, DB AU - Irvine, RF AU - Williams, RL PY - 2004/// ER -