title: Structural Insights into Cdk5 activation by a neuronal Cdk5 activator.
abstract: Although Cdk5 shows high sequence identity to Cdk1 and Cdk2, it can be fully activated by its neuronal activators p35/p25(nck5a) and p39(nck5ai) in a phosphorylation-independent manner. To understand structural basis of the Cdk5/p25(nck5a) activation, the complex is modelled to assume either an obstructed or an opened conformation based on X-ray structures of the unphosphorylated or the phosphorylated Cdk2/cyclin A complex, respectively. Comparison and analysis of the two models, along with mutagenesis studies of p25(nck5a), suggest that the opened form represents more closely the structure of active Cdk5/p25(nck5a). The results provide a rationale basis for understanding the phosphorylation-independent activation of Cdk5/p25(nck5a).
authors: The Proteomics Group, Institute of Molecular and Cell Biology, 30 Medical Drive, 117609, Singapore.
authors: H Y
authors: HY
authors: Lim
authors: K T
authors: KT
authors: Seow
authors: Q
authors: Q
authors: Li
authors: D
authors: D
authors: Kesuma
authors: J H
authors: JH
authors: Wang
authors: R Z
authors: RZ
authors: Qi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000378:metabolism*; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D020536:Enzyme Activators; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases