PDBsum entry 4rx9

Transferase/transferase inhibitor

PDB id: 4rx9

Contents

Protein chain

268 a.a.

Ligands

GOL

3YT

Waters ×204

PDB id:

4rx9

Name:

Transferase/transferase inhibitor

Title:

Syk catalytic domain complexed with a potent pyrimidine inhibitor

Structure:

Tyrosine-protein kinase syk. Chain: a. Synonym: spleen tyrosine kinase, p72-syk. Engineered: yes

Source:

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

Resolution:

1.75Å R-factor: 0.175 R-free: 0.197

Authors:

C.C.Lee

Key ref:

G.Thoma et al. (2015). Discovery and profiling of a selective and efficacious Syk inhibitor. J Med Chem, 58, 1950-1963. PubMed id: 25633741 DOI: 10.1021/jm5018863

Date:

09-Dec-14 Release date: 18-Mar-15

Protein chain

P43405  (KSYK_HUMAN) -  Tyrosine-protein kinase SYK from Homo sapiens

Seq: 635 a.a.

Struc: 268 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

DOI no: 10.1021/jm5018863

J Med Chem 58:1950-1963 (2015)

PubMed id: 25633741

Discovery and profiling of a selective and efficacious Syk inhibitor.

G.Thoma, A.B.Smith, M.J.van Eis, E.Vangrevelinghe, J.Blanz, R.Aichholz, A.Littlewood-Evans, C.C.Lee, H.Liu, H.G.Zerwes.

ABSTRACT

We describe the discovery of selective and potent Syk inhibitor 11, which exhibited favorable PK profiles in rat and dog and was found to be active in a collagen-induced arthritis model in rats. Compound 11 was selected for further profiling, but, unfortunately, in GLP toxicological studies it showed liver findings in rat and dog. Nevertheless, 11 could become a valuable tool compound to investigate the rich biology of Syk in vitro and in vivo.