PDBsum entry 3ewh

Transferase

PDB id: 3ewh

Contents

Protein chain

300 a.a. *

Ligands

K11

EDO

Waters ×268

* Residue conservation analysis

PDB id:

3ewh

Name:

Transferase

Title:

Crystal structure of the vegfr2 kinase domain in complex with a pyridyl-pyrimidine benzimidazole inhibitor

Structure:

Vascular endothelial growth factor receptor 2. Chain: a. Fragment: unp residues 815-939, 990-1171. Synonym: vegfr-2, kinase insert domain receptor, protein-tyrosine kinase receptor flk-1, cd309 antigen. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Organism_taxid: 9606. Gene: kdr, flk1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

1.60Å R-factor: 0.206 R-free: 0.234

Authors:

D.A.Whittington,A.M.Long,P.Rose,Y.Gu,H.Zhao

Key ref:

V.J.Cee et al. (2009). Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase. Bioorg Med Chem Lett, 19, 424-427. PubMed id: 19062275

Date:

15-Oct-08 Release date: 25-Aug-09

Protein chain

P35968  (VGFR2_HUMAN) -  Vascular endothelial growth factor receptor 2 from Homo sapiens

Seq: 1356 a.a.

Struc: 300 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

Added reference

Bioorg Med Chem Lett 19:424-427 (2009)

PubMed id: 19062275

Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase.

V.J.Cee, A.C.Cheng, K.Romero, S.Bellon, C.Mohr, D.A.Whittington, A.Bak, J.Bready, S.Caenepeel, A.Coxon, H.L.Deak, J.Fretland, Y.Gu, B.L.Hodous, X.Huang, J.L.Kim, J.Lin, A.M.Long, H.Nguyen, P.R.Olivieri, V.F.Patel, L.Wang, Y.Zhou, P.Hughes, S.Geuns-Meyer.

ABSTRACT

Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase.