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A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Chou, K. C. Watenpaugh, Keith David Heinrikson, Robert L. |
| Copyright Year | 1999 |
| Abstract | Tau protein kinase II (TPKII) is a heterodimer comprising a catalytic cyclin-dependent kinase subunit (Cdk5) and a regulatory protein called neuronal Cdk5 activator (Nck5a). TPKII is somewhat reminiscent, therefore, of the Cdk2-cyclin complex important in cell cycle regulation. In fact, although the amino acid sequence of Nck5a has little similarity to those of cyclins, recent experimental results obtained by site-directed mutagenesis studies have indicated that its activation domain, Nck5a*, may adopt a conformation of the cyclin-fold structure. Based on this structural inference, a 3-dimensional model of the Cdk5-Nck5a*-ATP complex was derived from the X-ray structure of Cdk2-cyclinA-ATP complex. The computed structure for TPKII is fully compatible with experimental data derived from studies of the Cdk5-Nck5a system, and also predicts which amino acid residues might be involved in formation of the Cdk5-Nck5a* interface and ATP binding pocket in TPKII. The computational structure also shows the interactive region of Nck5a* and the T-loop of Cdk5, a critical region in TPKII which functions as a gate-control-lever of the catalytic cleft. Furthermore, a physical mechanism is put forth to explain why the activation of TPKII is not dependent upon phosphorylation of the Cdk5 subunit, a puzzle long-standing in this area. These findings provide a model with which to consider design of compounds which might serve as inhibitors of TPKII. |
| File Format | PDF HTM / HTML |
| DOI | 10.1006/bbrc.1999.0792 |
| PubMed reference number | 10362524 |
| Journal | Medline |
| Volume Number | 259 |
| Issue Number | 2 |
| Alternate Webpage(s) | http://www.scirp.org/kcchou/papers/BBRC_1999_cdk5.pdf |
| Journal | Biochemical and biophysical research communications |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
