PDBsum entry 4dgg

Transferase

PDB id: 4dgg

Contents

Protein chains

261 a.a.

Ligands

I76 ×2

Waters ×13

PDB id:

4dgg

Name:

Transferase

Title:

C-src kinase domain in complex with rm-1-176

Structure:

Proto-oncogene tyrosine-protein kinase src. Chain: a, b. Fragment: kinase domain (unp residues 251-533). Synonym: proto-oncogenE C-src, pp60c-src, p60-src. Engineered: yes

Source:

Gallus gallus. Bantam,chickens. Organism_taxid: 9031. Gene: src. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.65Å R-factor: 0.210 R-free: 0.252

Authors:

E.A.Merritt,E.T.Larson

Key ref:

R.Krishnamurty et al. (2013). Active site profiling reveals coupling between domains in SRC-family kinases. Nat Chem Biol, 9, 43-50. PubMed id: 23143416

Date:

25-Jan-12 Release date: 10-Oct-12

Protein chains

P00523  (SRC_CHICK) -  Proto-oncogene tyrosine-protein kinase Src from Gallus gallus

Seq: 533 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

Nat Chem Biol 9:43-50 (2013)

PubMed id: 23143416

Active site profiling reveals coupling between domains in SRC-family kinases.

R.Krishnamurty, J.L.Brigham, S.E.Leonard, P.Ranjitkar, E.T.Larson, E.J.Dale, E.A.Merritt, D.J.Maly.

ABSTRACT

Protein kinases, key regulators of intracellular signal transduction, have emerged as an important class of drug targets. Chemical proteomic tools that facilitate the functional interrogation of protein kinase active sites are powerful reagents for studying the regulation of this large enzyme family and performing inhibitor selectivity screens. Here we describe a new crosslinking strategy that enables rapid and quantitative profiling of protein kinase active sites in lysates and live cells. Applying this methodology to the SRC-family kinases (SFKs) SRC and HCK led to the identification of a series of conformation-specific, ATP-competitive inhibitors that have a distinct preference for the autoinhibited forms of these kinases. Furthermore, we show that ligands that have this selectivity are able to modulate the ability of the regulatory domains of SRC and HCK to engage in intermolecular binding interactions. These studies provide insight into the regulation of this important family of tyrosine kinases.