PDBsum entry 3b2w

Transferase

PDB id: 3b2w

Contents

Protein chain

261 a.a. *

Ligands

9NH

Waters ×135

* Residue conservation analysis

PDB id:

3b2w

Name:

Transferase

Title:

Crystal structure of pyrimidine amide 11 bound to lck

Structure:

Proto-oncogene tyrosine-protein kinase lck. Chain: a. Fragment: lck kinase domain: residues 226-502. Synonym: p56-lck, lymphocyte cell-specific protein-tyrosine kinase, lsk, t cell-specific protein-tyrosine kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lck. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469. Expression_system_collection: insect cell

Resolution:

2.30Å R-factor: 0.230 R-free: 0.308

Authors:

X.Huang

Key ref:

H.L.Deak et al. (2008). N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR. Bioorg Med Chem Lett, 18, 1172-1176. PubMed id: 18083554 DOI: 10.1016/j.bmcl.2007.11.123

Date:

19-Oct-07 Release date: 18-Dec-07

Protein chain

P06239  (LCK_HUMAN) -  Tyrosine-protein kinase Lck from Homo sapiens

Seq: 509 a.a.

Struc: 261 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific 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

DOI no: 10.1016/j.bmcl.2007.11.123

Bioorg Med Chem Lett 18:1172-1176 (2008)

PubMed id: 18083554

N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR.

H.L.Deak, J.R.Newcomb, J.J.Nunes, C.Boucher, A.C.Cheng, E.F.DiMauro, L.F.Epstein, P.Gallant, B.L.Hodous, X.Huang, J.H.Lee, V.F.Patel, S.Schneider, S.M.Turci, X.Zhu.

ABSTRACT

N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective Lck inhibitors. This series of compounds derives its selectivity from a hydrogen bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data, structure-activity relationships, and the synthesis of these inhibitors are reported herein.