2c5v | pdb_00002c5v
DIFFERENTIAL BINDING OF INHIBITORS TO ACTIVE AND INACTIVE CDK2 PROVIDES INSIGHTS FOR DRUG DESIGN
| |||||||||||||
| 2c5v, resolution 2.90Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sites: | AC1 | ||||||||||||
| Ligands: | AB7, CK4, NH2, PFF | ||||||||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
The cyclin-dependent kinases (CDKs) have been characterized in complex with a variety of inhibitors, but the majority of structures solved are in the inactive form. We have solved the structures of six inhibitors in both the monomeric CDK2 and binary CDK2/cyclinA complexes and demonstrate that significant differences in ligand binding occur depending on the activation state. The binding mode of two ligands in particular varies substantially in active and inactive CDK2. Furthermore, energetic analysis of CDK2/cyclin/inhibitors demonstrates that a good correlation exists between the in vitro potency and the calculated energies of interaction, but no such relationship exists for CDK2/inhibitor structures. These results confirm that monomeric CDK2 ligand complexes do not fully reflect active conformations, revealing significant implications for inhibitor design while also suggesting that the monomeric CDK2 conformation can be selectively inhibited.
About this Structure
2C5V is a Protein complex structure of sequences from Homo sapiens. This structure supersedes the now removed PDB entry 1OKU. Full crystallographic information is available from OCA.
Reference
Differential binding of inhibitors to active and inactive CDK2 provides insights for drug design., Kontopidis G, McInnes C, Pandalaneni SR, McNae I, Gibson D, Mezna M, Thomas M, Wood G, Wang S, Walkinshaw MD, Fischer PM, Chem Biol. 2006 Feb;13(2):201-11. PMID:16492568
Page seeded by OCA on Mon Mar 31 02:16:49 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Non-specific serine/threonine protein kinase
- Protein complex
- Fischer, P M.
- Gibson, D.
- Kontopidis, G.
- Mcinnes, C.
- Mcnae, I.
- Mezna, M.
- Pandalaneni, S R.
- Thomas, M.
- Walkinshaw, M D.
- Wang, S.
- Wood, G.
- Atp-binding
- Cell cycle
- Cell division
- Complex (kinase/cyclin)
- Complex (transferase/cyclin)
- Cycin some
- Cyclin
- Drug design
- Kinase
- Ligand exchange
- Mitosis
- Nucleotide-binding
- Phosphorylation
- Serine/threonine-protein kinase
- Transferase
