1BYG

KINASE DOMAIN OF HUMAN C-TERMINAL SRC KINASE (CSK) IN COMPLEX WITH INHIBITOR STAUROSPORINE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.199 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure of the protein tyrosine kinase domain of C-terminal Src kinase (CSK) in complex with staurosporine.

Lamers, M.B.Antson, A.A.Hubbard, R.E.Scott, R.K.Williams, D.H.

(1999) J Mol Biol 285: 713-725

  • DOI: https://doi.org/10.1006/jmbi.1998.2369
  • Primary Citation of Related Structures:  
    1BYG

  • PubMed Abstract: 

    The crystal structure of the kinase domain of C-terminal Src kinase (CSK) has been determined by molecular replacement, co-complexed with the protein kinase inhibitor staurosporine (crystals belong to the space group P21212 with a=44.5 A, b=120.6 A, c=48.3 A). The final model of CSK has been refined to an R-factor of 19.9 % (Rfree=28.7 %) at 2.4 A resolution. The structure consists of a small, N-terminal lobe made up mostly of a beta-sheet, and a larger C-terminal lobe made up mostly of alpha-helices. The structure reveals atomic details of interactions with staurosporine, which binds in a deep cleft between the lobes. The polypeptide chain fold of CSK is most similar to c-Src, Hck and fibroblast growth factor receptor 1 kinase (FGFR1K) and most dissimilar to insulin receptor kinase (IRK). Interactions between the N and C-terminal lobe are mediated by the bound staurosporine molecule and by hydrogen bonds. In addition, there are several water molecules forming lobe-bridging hydrogen bonds, which may be important for maintaining the catalytic integrity of the kinase. Furthermore, the conserved Lys328 and Glu267 residues utilise water in the formation of a molecular pivot which is essential in allowing relative movement of the N and C-terminal lobes. An analysis of the residues around the ATP-binding site reveals structural differences with other protein tyrosine kinases. Most notable of these are different orientations of the conserved residues Asp332 and Phe333, suggesting that inhibitor binding proceeds via an induced fit. These structural observations have implications for understanding protein tyrosine kinase catalytic mechanisms and for the design of ATP-mimicking inhibitors of protein kinases.


  • Organizational Affiliation

    Peptide Therapeutics, 321 Cambridge Science Park, Cambridge, CB4 4WG, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (C-TERMINAL SRC KINASE)278Homo sapiensMutation(s): 0 
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P41240 (Homo sapiens)
Explore P41240 
Go to UniProtKB:  P41240
PHAROS:  P41240
GTEx:  ENSG00000103653 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP41240
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
STU
Query on STU

Download Ideal Coordinates CCD File 
B [auth A]STAUROSPORINE
C28 H26 N4 O3
HKSZLNNOFSGOKW-FYTWVXJKSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.287 
  • R-Value Work: 0.199 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.49α = 90
b = 120.58β = 90
c = 48.29γ = 90
Software Package:
Software NamePurpose
CCP4model building
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
CCP4phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-10-14
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description