1XBA

Crystal structure of apo syk tyrosine kinase domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.231 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase.

Atwell, S.Adams, J.M.Badger, J.Buchanan, M.D.Feil, I.K.Froning, K.J.Gao, X.Hendle, J.Keegan, K.Leon, B.C.Muller-Deickmann, H.J.Nienaber, V.L.Noland, B.W.Post, K.Rajashankar, K.R.Ramos, A.Russell, M.Burley, S.K.Buchanan, S.G.

(2004) J Biol Chem 279: 55827-55832

  • DOI: https://doi.org/10.1074/jbc.M409792200
  • Primary Citation of Related Structures:  
    1XBA, 1XBB, 1XBC

  • PubMed Abstract: 

    Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of two tyrosine residues in the activation loop of the Syk kinase catalytic domain is necessary for signaling, a phenomenon typical of tyrosine kinase family members. Syk in vitro enzyme activity, however, does not depend on phosphorylation (activation loop tyrosine --> phenylalanine mutants retain catalytic activity). We have determined the x-ray structure of the unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a conformation of the activation loop typically seen only in activated, phosphorylated tyrosine kinases, explaining why Syk does not require phosphorylation for activation. We also demonstrate that Gleevec (STI-571, Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact cis-conformation that differs dramatically from the binding mode observed with unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding suggests the existence of two distinct Gleevec binding modes: an extended, trans-conformation characteristic of tight binding to the inactive conformation of a protein kinase and a second compact, cis-conformation characteristic of weaker binding to the active conformation. Finally, the Syk-bound cis-conformation of Gleevec bears a striking resemblance to the rigid structure of the nonspecific, natural product kinase inhibitor staurosporine.


  • Organizational Affiliation

    Structural GenomiX, Inc., 10505 Roselle Street, San Diego, CA 92121, USA. satwell@stromix.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase SYK291Homo sapiensMutation(s): 0 
Gene Names: SYK
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P43405 (Homo sapiens)
Explore P43405 
Go to UniProtKB:  P43405
PHAROS:  P43405
GTEx:  ENSG00000165025 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP43405
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.231 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.785α = 90
b = 84.721β = 90
c = 90.186γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
TRUNCATEdata reduction
REFMACrefinement
CCP4data scaling
TRUNCATEdata scaling

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2004-11-02
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2021-02-03
    Changes: Database references, Structure summary
  • Version 1.5: 2024-02-14
    Changes: Data collection, Database references