1PF8

Crystal Structure of Human Cyclin-Dependent Kinase 2 Complexed with a Nucleoside Inhibitor

Summary for 1PF8

• Entry DOI: 10.2210/pdb1pf8/pdb
• Related: 1HCK
• Descriptor: Cell division protein kinase 2, (3Z)-3-(1H-IMIDAZOL-5-YLMETHYLENE)-5-METHOXY-1H-INDOL-2(3H)-ONE (2 entities in total)
• Functional Keywords: transferase, serine/threonine protein kinase, atp-binding, cell cycle, cell division, mitosis, phosphorylation, su9516, inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941
• Total number of polymer chains: 1
• Total formula weight: 34217.73

Authors

Moshinsky, D.J.,Bellamacina, R.C.,Boisvert, D.C.,Huang, P.,Hui, T.,Jancarik, J.,Kim, S.H.,Rice, A.G. (deposition date: 2003-05-24, release date: 2003-12-23, Last modification date: 2023-08-16)

Primary citation

Moshinsky, D.J.,Bellamacina, C.R.,Boisvert, D.C.,Huang, P.,Hui, T.,Jancarik, J.,Kim, S.H.,Rice, A.G.
SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2.
Biochem.Biophys.Res.Commun., 310:1026-1031, 2003

PubMed Abstract: SU9516 is a 3-substituted indolinone compound with demonstrated potent and selective inhibition toward cyclin dependent kinases (cdks). Here, we describe the kinetic characterization of this inhibition with respect to cdk2, 1, and 4, along with the crystal structure in complex with cdk2. The molecule is competitive with respect to ATP for cdk2/cyclin A, with a K(i) value of 0.031 microM. Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. In contrast, the compound exhibited non-competitive inhibition with respect to ATP toward cdk4/cyclin D1, with a 45-fold reduced potency. The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. This study should aid in the development of more potent and selective cdk inhibitors for potential therapeutic agents.

PubMed: 14550307
DOI: 10.1016/j.bbrc.2003.09.114

Experimental method

X-RAY DIFFRACTION (2.51 Å)