2iw6 | pdb_00002iw6
| |||||||||||||
| 2iw6, resolution 2.30Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sites: | AC1 | ||||||||||||
| Ligands: | MG, QQ2, SGM, TPO | ||||||||||||
| 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 | ||||||||||||
STRUCTURE OF HUMAN THR160-PHOSPHO CDK2-CYCLIN A COMPLEXED WITH A BISANILINOPYRIMIDINE INHIBITOR
Overview
Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent cyclin-dependent kinase 4 residues, namely F82H, L83V, H84D, and K89T. Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. The results indicate that certain residues that are not frequently considered in structure-aided kinase inhibitor design have an important role to play.
About this Structure
2IW6 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity., Pratt DJ, Bentley J, Jewsbury P, Boyle FT, Endicott JA, Noble ME, J Med Chem. 2006 Sep 7;49(18):5470-7. PMID:16942020
Page seeded by OCA on Mon Mar 31 03:49:27 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Non-specific serine/threonine protein kinase
- Protein complex
- Bentley, J.
- Boyle, F T.
- Endicott, J A.
- Jewsbury, P.
- Noble, M E.M.
- Pratt, D J.
- Atp-binding
- Cell cycle
- Cell cycle complex
- Cell division
- Cyclin
- Kinase
- Mitosis
- Nucleotide-binding
- Phosphorylation
- Polymorphism
- Serine-threonine-protein kinase
- Serine/threonine-protein kinase
- Transferase
