PDBsum entry 2j9m

Transferase

PDB id: 2j9m

Contents

Protein chain

275 a.a. *

Ligands

PY8

Waters ×16

* Residue conservation analysis

PDB id:

2j9m

Name:

Transferase

Title:

Crystal structure of cdk2 in complex with macrocyclic aminopyrimidine

Structure:

Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase, cdk2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.50Å R-factor: 0.219 R-free: 0.294

Authors:

M.Schaefer,U.Luecking,G.Siemeister,H.Briem,M.Krueger,P.Lienau, R.Jautelat

Key ref:

U.Lücking et al. (2007). Macrocyclic aminopyrimidines as multitarget CDK and VEGF-R inhibitors with potent antiproliferative activities. Chemmedchem, 2, 63-77. PubMed id: 17131463

Date:

13-Nov-06 Release date: 06-Nov-07

Protein chain

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

Seq: 298 a.a.

Struc: 275 a.a.

Enzyme reactions

• Enzyme class: 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

Chemmedchem 2:63-77 (2007)

PubMed id: 17131463

Macrocyclic aminopyrimidines as multitarget CDK and VEGF-R inhibitors with potent antiproliferative activities.

U.Lücking, G.Siemeister, M.Schäfer, H.Briem, M.Krüger, P.Lienau, R.Jautelat.

ABSTRACT

X-ray structures from CDK2-aminopyrimidine inhibitor complexes led to the idea to stabilize the active conformation of aminopyrimidine inhibitors by incorporating the recognition site into a macrocyclic framework. A modular synthesis approach that relies on a new late-stage macrocyclization protocol that enables fast and efficient synthesis of macrocyclic aminopyrimidines was developed. A set of structurally diverse derivatives was prepared. Macrocyclic aminopyrimidines were shown to be multitarget inhibitors of CDK1/2 and VEGF-RTKs. In addition, potent antiproliferative activities toward various human tumor cells and a human tumor xenograft model were demonstrated.