PDBsum entry 3ej1

Transferase/cell cycle

PDB id: 3ej1

Contents

Protein chains

295 a.a. *

258 a.a. *

Ligands

5BP ×2

* Residue conservation analysis

PDB id:

3ej1

Name:

Transferase/cell cycle

Title:

Cdk2/cyclina complexed with a pyrazolopyridazine inhibitor

Structure:

Cell division protein kinase 2. Chain: a, c. Synonym: p33 protein kinase. Engineered: yes. Cyclin-a2. Chain: b, d. Fragment: unp residues 113-432. Synonym: cyclin-a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: ccna2, ccn1, ccna. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.22Å R-factor: 0.221 R-free: 0.259

Authors:

K.Stevens,M.Reno,J.Alberti,D.Price,L.Kane-Carson,V.Knick,L.Shewchuk, A.Hassell,J.Veal,M.Peel

Key ref:

K.L.Stevens et al. (2008). Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors. Bioorg Med Chem Lett, 18, 5758-5762. PubMed id: 18835709

Date:

17-Sep-08 Release date: 21-Oct-08

Protein chains

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

Seq: 298 a.a.

Struc: 295 a.a.

Protein chains

P20248  (CCNA2_HUMAN) -  Cyclin-A2 from Homo sapiens

Seq: 432 a.a.

Struc: 258 a.a.

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

Bioorg Med Chem Lett 18:5758-5762 (2008)

PubMed id: 18835709

Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors.

K.L.Stevens, M.J.Reno, J.B.Alberti, D.J.Price, L.S.Kane-Carson, V.B.Knick, L.M.Shewchuk, A.M.Hassell, J.M.Veal, S.T.Davis, R.J.Griffin, M.R.Peel.

ABSTRACT

A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C(2)- and C(6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3beta.