PDBsum entry 1yol

Transferase

PDB id: 1yol

Contents

Protein chains

256 a.a. *

Ligands

S03 ×2

Waters ×256

* Residue conservation analysis

PDB id:

1yol

Name:

Transferase

Title:

Crystal structure of src kinase domain in complex with cgp77675

Structure:

Proto-oncogene tyrosine-protein kinase src. Chain: a, b. Fragment: src kinase domain. Synonym: p60-src, c-src. Engineered: yes. Mutation: yes

Source:

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

Resolution:

2.30Å R-factor: 0.196 R-free: 0.247

Authors:

C.B.Breitenlechner,N.A.Kairies,K.Honold,S.Scheiblich,H.Koll, E.Greiter,S.Koch,W.Schaefer,R.Huber,R.A.Engh

Key ref:

C.B.Breitenlechner et al. (2005). Crystal structures of active SRC kinase domain complexes. J Mol Biol, 353, 222-231. PubMed id: 16168436 DOI: 10.1016/j.jmb.2005.08.023

Date:

27-Jan-05 Release date: 27-Jan-06

Protein chains

P12931  (SRC_HUMAN) -  Proto-oncogene tyrosine-protein kinase Src from Homo sapiens

Seq: 536 a.a.

Struc: 256 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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.jmb.2005.08.023

J Mol Biol 353:222-231 (2005)

PubMed id: 16168436

Crystal structures of active SRC kinase domain complexes.

C.B.Breitenlechner, N.A.Kairies, K.Honold, S.Scheiblich, H.Koll, E.Greiter, S.Koch, W.Schäfer, R.Huber, R.A.Engh.

ABSTRACT

c-Src was the first proto-oncoprotein to be identified, and has become the focus of many drug discovery programs. Src structures of a major inactive form have shown how the protein kinase is rigidified by several interdomain interactions; active configurations of Src are generated by release from this "assembled" or "bundled" form. Despite the importance of Src as a drug target, there is relatively little structural information available regarding the presumably more flexible active forms. Here we report three crystal structures of a dimeric active c-Src kinase domain, in an apo and two ligand complexed forms, with resolutions ranging from 2.9A to 1.95A. The structures show how the kinase domain, in the absence of the rigidifying interdomain interactions of the inactivation state, adopts a more open and flexible conformation. The ATP site inhibitor CGP77675 binds to the protein kinase with canonical hinge hydrogen bonds and also to the c-Src specific threonine 340. In contrast to purvalanol B binding in CDK2, purvalanol A binds in c-Src with a conformational change in a more open ATP pocket.

Selected figure(s)

Figure 1.
Figure 1. Chemical structures of inhibitors (a) purvalanol A and (b) CGP77675 used for co-crystallization.

Figure 5.
Figure 5. Binding of the pyrrolo-pyrimidine inhibitor CGP77675 to the kinase domain of Src. (a) Stereo view of the inhibitor binding pocket with Sim weighted electron density maps of the refined complex of CGP77675 and the kinase domain of Src at 2.3 Å resolution (light brown, 2mF[o] -dF[c], contoured at 1s) and an omit map (dark brown, mF[o] -dF[c], contoured at 2s) prior to building inhibitor into the model. (b) Stereo view of the inhibitor binding pocket: molecules A and B of the asymmetric unit have been superimposed. They show the same basic binding mode; the differences in the 4-hydroxy-piperidine-ethyl substituent are well defined by electron density maps.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 353, 222-231) copyright 2005.

Figures were selected by an automated process.