PDBsum entry 1qcf

Tyrosine kinase

PDB id: 1qcf

Contents

Protein chain

450 a.a. *

Ligands

PP1

Waters ×312

* Residue conservation analysis

PDB id:

1qcf

Name:

Tyrosine kinase

Title:

Crystal structure of hck in complex with a src family-selective tyrosine kinase inhibitor

Structure:

Tyrosine-protein kinase hck. Chain: a. Fragment: sh3-sh2-kinase-high affinity tail. Synonym: hematopoietic cell kinase,hemopoietic cell kinase,p59- hck/p60-hck,p59hck,p61hck. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hck.

Resolution:

2.00Å R-factor: 0.215 R-free: 0.257

Authors:

T.Schindler,F.Sicheri,A.Pico,A.Gazit,A.Levitzki,J.Kuriyan

Key ref:

T.Schindler et al. (1999). Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor. Mol Cell, 3, 639-648. PubMed id: 10360180 DOI: 10.1016/S1097-2765(00)80357-3

Date:

04-May-99 Release date: 08-Jun-99

Protein chain

P08631  (HCK_HUMAN) -  Tyrosine-protein kinase HCK from Homo sapiens

Seq: 526 a.a.

Struc: 450 a.a.*

* PDB and UniProt seqs differ at 7 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/S1097-2765(00)80357-3

Mol Cell 3:639-648 (1999)

PubMed id: 10360180

Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor.

T.Schindler, F.Sicheri, A.Pico, A.Gazit, A.Levitzki, J.Kuriyan.

ABSTRACT

The crystal structure of the autoinhibited form of Hck has been determined at 2.0 A resolution, in complex with a specific pyrazolo pyrimidine-type inhibitor, PP1. The activation segment, a key regulatory component of the catalytic domain, is unphosphorylated and is visualized in its entirety. Tyr-416, the site of activating autophosphorylation in the Src family kinases, is positioned such that access to the catalytic machinery is blocked. PP1 is bound at the ATP-binding site of the kinase, and a methylphenyl group on PP1 is inserted into an adjacent hydrophobic pocket. The enlargement of this pocket in autoinhibited Src kinases suggests a route toward the development of inhibitors that are specific for the inactive forms of these proteins.

Selected figure(s)

Figure 4.
Figure 4. Interdependence of the Conformations of Helix αC and the Activation SegmentThe catalytic domain of inactive Hck is shown superimposed on that of active Lck ([45]) (A) and of inactive Cdk2 (B) ( [6]). The structural alignments are based on the C-terminal lobe in (A) and on the β strands in the N-terminal lobe of the kinase domains in (B). Helix αC (α1 in Cdk2) and the activation segment are colored in blue, red, and green for Hck, Lck, and Cdk2, respectively. The figure was generated using RIBBONS ( [5]).

Figure 7.
Figure 7. PP1 Leaves Unfilled a Cavity in Inactive Hck(A) Structure of the PP1-binding region in inactive Hck. PP1 binding creates a cavity (yellow surface) in the back of the ATP-binding site, where two well-ordered water molecules (W1 and W2) are found.(B) The same cavity (yellow) viewed from the top of the N-terminal lobe of the catalytic domain. The collapse of this cavity in active Lck is indicated by showing helix αC as found in the structure of Lck (PDB code 3lck; [45]), drawn in orange.

The above figures are reprinted by permission from Cell Press: Mol Cell (1999, 3, 639-648) copyright 1999.

Figures were selected by an automated process.