Please use this identifier to cite or link to this item: https://doi.org/10.1021/bi700890t
Title: The activation and inhibition of cyclin-dependent kinase-5 by phosphorylation
Authors: Zhang, B. 
Tan, V.B.C. 
Lim, K.M. 
Tay, T.E. 
Issue Date: 25-Sep-2007
Source: Zhang, B., Tan, V.B.C., Lim, K.M., Tay, T.E. (2007-09-25). The activation and inhibition of cyclin-dependent kinase-5 by phosphorylation. Biochemistry 46 (38) : 10841-10851. ScholarBank@NUS Repository. https://doi.org/10.1021/bi700890t
Abstract: Despite the very similar 3-dimensional structures as reflected by the more than 60% identity in amino acid sequences, CDK2 and CDK5 have very different functions and characteristics. Phosphorylation on a conserved Thr14 can inhibit activities of both the kinases, but phosphorylating another conserved Tyr15, however, can lead to totally opposite inhibition and stimulation consequences in CDK2 and CDK5. Our molecular dynamics (MD) simulations suggest a similar inhibition mechanism of phosphorylation on the Thr14 as in the CDK2 system. In both the systems, the kinase activities are inhibited by the phosphorylation because it causes ATP phosphate moiety misalignment and changes in the Mg 2+ ion coordination sphere, which have been proven to be critical for the phosphate group of the ATP transferring to the hydroxyl group on the serine in the substrate peptide. The calculations indicate that ATP adopts a more favorable conformation and location in the phosphorylated Tyr15 complex to facilitate the interactions with the substrate and the Mg2+ is wrapped more strongly by the phosphate group than in the unphosphorylated system, which might be favored by the transfer reaction. © 2007 American Chemical Society.
Source Title: Biochemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/85747
ISSN: 00062960
DOI: 10.1021/bi700890t
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