1H4L

Structure and regulation of the CDK5-p25(nck5a) complex

Summary for 1H4L

• Entry DOI: 10.2210/pdb1h4l/pdb
• Related: 1LFR
• Descriptor: CELL DIVISION PROTEIN KINASE 5, CYCLIN-DEPENDENT KINASE 5 ACTIVATOR (3 entities in total)
• Functional Keywords: kinase-kinase activator complex, complex(cyclins-cdk), cyclins, cyclin-dependent kinases, cdk5, p35, p25, transferase, atp-binding, cell cycle, cell division, phosphorylation, kinase/kinase activator
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 100764.27

Authors

Tarricone, C.,Dhavan, R.,Peng, J.,Areces, L.B.,Tsai, L.-H.,Musacchio, A. (deposition date: 2001-05-11, release date: 2002-08-14, Last modification date: 2023-12-13)

Primary citation

Tarricone, C.,Dhavan, R.,Peng, J.,Areces, L.B.,Tsai, L.-H.,Musacchio, A.
Structure and Regulation of the Cdk5-P25(Nck5A) Complex
Mol.Cell, 8:657-, 2001

PubMed Abstract: CDK5 plays an indispensable role in the central nervous system, and its deregulation is involved in neurodegeneration. We report the crystal structure of a complex between CDK5 and p25, a fragment of the p35 activator. Despite its partial structural similarity with the cyclins, p25 displays an unprecedented mechanism for the regulation of a cyclin-dependent kinase. p25 tethers the unphosphorylated T loop of CDK5 in the active conformation. Residue Ser159, equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35 interaction. Its substitution with threonine prevents p35 binding, while the presence of alanine affects neither binding nor kinase activity. Finally, we provide evidence that the CDK5-p25 complex employs a distinct mechanism from the phospho-CDK2-cyclin A complex to establish substrate specificity.

PubMed: 11583627
DOI: 10.1016/S1097-2765(01)00343-4

Experimental method

X-RAY DIFFRACTION (2.65 Å)