title: Homology model of the CDK1/cyclin B complex.
abstract: 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.
authors.affiliation: Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD 21702, USA. mcgrath@ncifcrf.gov
authors.forename: Connor F
authors.initials: CF
authors.lastname: McGrath
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Pattabiraman
authors.forename: Glen E
authors.initials: GE
authors.lastname: Kellogg
authors.forename: Thomas
authors.initials: T
authors.lastname: Lemcke
authors.forename: Conrad
authors.initials: C
authors.lastname: Kunick
authors.forename: Edward A
authors.initials: EA
authors.lastname: Sausville
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Zaharevitz
authors.forename: Rick
authors.initials: R
authors.lastname: Gussio
mesh_terms: 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
chemical_list: D019926:Cyclin B; D000255:Adenosine Triphosphate; D016203:CDC2 Protein Kinase