Homology model of the CDK1/cyclin B complex.
We describe a refined homology model of a CDK1/cyclin B complex that was previously used for the structure-based optimization of the Paullone class of inhibitors. The preliminary model was formed from the homologous regions of the deposited CDK2/cyclin A crystal structure. Further refinement of the CDK1/cyclin B complex was accomplished using molecular mechanics and hydropathic analysis with a protocol of constraints and local geometry searches. For the most part, our CKD1/cyclin B homology model is very similar to the high resolution CDK2/cyclin A crystal structure regarding secondary and tertiary features. However, minor discrepancies between the two kinase structures suggest the possibility that ligand design may be specifically tuned for either CDK1 or CDK2. Our examination of the CDK1/cyclin B model includes a comparison with the CDK2/cyclin A crystal structure in the PSTAIRE interface region, connecting portions to the ATP binding domain, as well as the ATP binding site itself.
McGrath
Connor F
CF
Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702, USA. mcgrath@ncifcrf.gov
Pattabiraman
Nagarajan
N
Kellogg
Glen E
GE
Lemcke
Thomas
T
Kunick
Conrad
C
Sausville
Edward A
EA
Zaharevitz
Daniel W
DW
Gussio
Rick
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000737:chemistry* / Q000378:metabolism; D019926:Cyclin B / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013215:Starfish / Q000201:enzymology; D040681:Structural Homology, Protein
D019926:Cyclin B; D000255:Adenosine Triphosphate; D016203:CDC2 Protein Kinase