Understanding inositol pyrophosphate metabolism and function: Kinetic characterization of the DIPPs

作者：Kilari Rajagopal S; Weaver Jeremy D; Shears Stephen B^*; Safrany Stephen T

来源：FEBS LETTERS, 2013, 587(21): 3464-3470.

DOI：10.1016/j.febslet.2013.08.035

• Nudix
• Diphosphoinositol
• Phosphohydrolase
• CDK5RAP1

We illuminate the metabolism and the cell-signaling activities of inositol pyrophosphates, by showing that regulation of yeast cyclin-kinase by 1-InsP(7) is not conserved for mammalian CDK5, and by kinetically characterizing Ddp1p/DIPP-mediated dephosphorylation of 1-InsP(7), 5-InsP(7) and InsP(8). Each phosphatase exhibited similar Km values for every substrate (range: 35-148 nM). The rank order of k(cat) values (1-InsP(7) > 5-InsP(7) = InsP(8)) was identical for each enzyme, although DIPP1 was 10- to 60-fold more active than DIPP2 alpha/beta and DIPP3 alpha/beta. We demonstrate InsP(8) dephosphorylation preferentially progresses through 1-InsP(7). Conversely, we conclude that the more metabolically and functionally significant steady-state route of InsP(8) synthesis proceeds via 5-InsP(7). Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.

• 出版日期2013-11-1