PDBsum entry 3mpm

Transferase

PDB id: 3mpm

Contents

Protein chain

257 a.a. *

Ligands

5LK

EDO

Waters ×258

* Residue conservation analysis

PDB id:

3mpm

Name:

Transferase

Title:

Lck complexed with a pyrazolopyrimidine

Structure:

Tyrosine-protein kinase lck. Chain: a. Fragment: unp residues 237-501. Synonym: proto-oncogene lck, lymphocyte cell-specific protein- tyrosine kinase, p56-lck, lsk, t cell-specific protein-tyrosine kinase. Engineered: yes. Mutation: yes

Source:

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

Resolution:

1.95Å R-factor: 0.172 R-free: 0.213

Authors:

S.W.Cowan-Jacob,G.Rummel

Key ref:

N.Gommermann et al. (2010). New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck. Bioorg Med Chem Lett, 20, 3628-3631. PubMed id: 20483608

Date:

27-Apr-10 Release date: 02-Jun-10

Protein chain

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

Seq: 509 a.a.

Struc: 257 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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

Bioorg Med Chem Lett 20:3628-3631 (2010)

PubMed id: 20483608

New pyrazolo[1,5a]pyrimidines as orally active inhibitors of Lck.

N.Gommermann, P.Buehlmayer, A.von Matt, W.Breitenstein, K.Masuya, B.Pirard, P.Furet, S.W.Cowan-Jacob, G.Weckbecker.

ABSTRACT

A novel series of pyrazolo[1,5a]pyrimidines was optimized to target lymphocyte-specific kinase (Lck). An efficient synthetic route was developed and SAR studies toward activity and selectivity are described, leading to Lck inhibitors with enzymatic, cellular and in vivo potency.