PDBsum entry 2g9x

Transferase/cell cycle

PDB id: 2g9x

Contents

Protein chains

299 a.a. *

262 a.a. *

275 a.a. *

Ligands

NU5 ×2

Waters ×161

* Residue conservation analysis

PDB id:

2g9x

Name:

Transferase/cell cycle

Title:

Structure of thr 160 phosphorylated cdk2/cyclin a in complex with the inhibitor nu6271

Structure:

Cell division protein kinase 2. Chain: a, c. Synonym: p33 protein kinase. Engineered: yes. Cyclin-a2. Chain: b, d. Synonym: cyclin-a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: escherichia coli. Expression_system_taxid: 562. Bos taurus. Cattle. Organism_taxid: 9913.

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.219 R-free: 0.265

Authors:

A.Echalier,J.A.Endicott,M.E.Noble

Key ref:

R.J.Griffin et al. (2006). Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination. J Am Chem Soc, 128, 6012-6013. PubMed id: 16669651 DOI: 10.1021/ja060595j

Date:

07-Mar-06 Release date: 23-May-06

Protein chain

P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2 from Homo sapiens

Seq: 298 a.a.

Struc: 299 a.a.*

Protein chains

P30274  (CCNA2_BOVIN) -  Cyclin-A2 from Bos taurus

Seq: 430 a.a.

Struc: 262 a.a.*

Protein chain

P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2 from Homo sapiens

Seq: 298 a.a.

Struc: 275 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, C: E.C.2.7.11.22 - cyclin-dependent kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/ja060595j

J Am Chem Soc 128:6012-6013 (2006)

PubMed id: 16669651

Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination.

R.J.Griffin, A.Henderson, N.J.Curtin, A.Echalier, J.A.Endicott, I.R.Hardcastle, D.R.Newell, M.E.Noble, L.Z.Wang, B.T.Golding.

ABSTRACT

beta-Piperidinoethylsulfides are oxidized by m-chloroperbenzoic acid to intermediates containing both N-oxide and sulfone functions. These undergo a Cope-type elimination to a vinylsulfone that can be captured by amines to afford beta-aminoethylsulfones. When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. One of the most potent inhibitors (IC50 = 45 nM) contained a N-3-hydroxypropyl group on the aminoethylsulfonyl substituent. The crystal structure of this inhibitor bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen bonds. The synthetic methodology developed can be utilized in multiple-parallel format and has numerous potential applications in medicinal chemistry.