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PDBsum entry 1skj
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Tyrosine-protein kinase PDB id
1skj

 

 

 

 

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Contents
Protein chain
102 a.a. *
Ligands
UR2
Waters ×183
* Residue conservation analysis
PDB id:
1skj
Name: Tyrosine-protein kinase
Title: Cocrystal structure of urea-substituted phosphopeptide complex
Structure: Pp60 v-src tyrosine kinase transforming protein. Chain: a. Fragment: sh2 domain. Synonym: src sh2. Engineered: yes. Mutation: yes
Source: Rous sarcoma virus. Organism_taxid: 11886. Strain: schmidt-ruppin strain a. Cell_line: jm 83. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: jm83.
Resolution:
2.00Å     R-factor:   0.200     R-free:   0.275
Authors: D.R.Holland,J.R.Rubin
Key ref: M.S.Plummer et al. (1997). Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand. J Med Chem, 40, 3719-3725. PubMed id: 9371236 DOI: 10.1021/jm970402q
Date:
18-Sep-97     Release date:   25-Feb-98    
PROCHECK
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 Headers
 References

Protein chain
P00524  (SRC_RSVSA) -  Tyrosine-protein kinase transforming protein Src from Rous sarcoma virus subgroup A (strain Schmidt-Ruppin)
Seq:
Struc: 		 
Seq:
Struc: 		526 a.a.
102 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.2  - non-specific protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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: 10.1021/jm970402q J Med Chem 40:3719-3725 (1997)
PubMed id: 9371236  
 
 
Design, synthesis, and cocrystal structure of a nonpeptide Src SH2 domain ligand.
M.S.Plummer, D.R.Holland, A.Shahripour, E.A.Lunney, J.H.Fergus, J.S.Marks, P.McConnell, W.T.Mueller, T.K.Sawyer.
 
  ABSTRACT  
 
The specific association of an SH2 domain with a phosphotyrosine (pTyr)-containing sequence of another protein precipitates a cascade of intracellular molecular interactions (signals) which effect a wide range of intracellular processes. The nonreceptor tyrosine kinase Src, which has been associated with breast cancer and osteoporosis, contains an SH2 domain. Inhibition of Src SH2-phosphoprotein interactions by small molecules will aid biological proof-of-concept studies which may lead to the development of novel therapeutic agents. Structure-based design efforts have focused on reducing the size and charge of Src SH2 ligands while increasing their ability to penetrate cells and reach the intracellular Src SH2 domain target. In this report we describe the synthesis, binding affinity, and Src SH2 cocrystal structure of a small, novel, nonpeptide, urea-containing SH2 domain ligand.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19334714 P.K.Mandal, D.Limbrick, D.R.Coleman, G.A.Dyer, Z.Ren, J.S.Birtwistle, C.Xiong, X.Chen, J.M.Briggs, and J.S.McMurray (2009).
Conformationally constrained peptidomimetic inhibitors of signal transducer and activator of transcription. 3: Evaluation and molecular modeling.
  J Med Chem, 52, 2429-2442.  
11746693 G.M.Verkhivker, D.Bouzida, D.K.Gehlhaar, P.A.Rejto, L.Schaffer, S.Arthurs, A.B.Colson, S.T.Freer, V.Larson, B.A.Luty, T.Marrone, and P.W.Rose (2001).
Hierarchy of simulation models in predicting molecular recognition mechanisms from the binding energy landscapes: structural analysis of the peptide complexes with SH2 domains.
  Proteins, 45, 456-470.  
11682324 M.Vidal, V.Gigoux, and C.Garbay (2001).
SH2 and SH3 domains as targets for anti-proliferative agents.
  Crit Rev Oncol Hematol, 40, 175-186.  
  11106171 D.A.Henriques, J.E.Ladbury, and R.M.Jackson (2000).
Comparison of binding energies of SrcSH2-phosphotyrosyl peptides with structure-based prediction using surface area based empirical parameterization.
  Protein Sci, 9, 1975-1985.  
10679371 J.C.Way (2000).
Covalent modification as a strategy to block protein-protein interactions with small-molecule drugs.
  Curr Opin Chem Biol, 4, 40-46.  
11121839 M.Susva, M.Missbach, and J.Green (2000).
Src inhibitors: drugs for the treatment of osteoporosis, cancer or both?
  Trends Pharmacol Sci, 21, 489-495.  
10021933 J.Schoepfer, H.Fretz, B.Gay, P.Furet, C.García-Echeverría, N.End, and G.Caravatti (1999).
Highly potent inhibitors of the Grb2-SH2 domain.
  Bioorg Med Chem Lett, 9, 221-226.  
9799501 J.M.Bradshaw, and G.Waksman (1998).
Calorimetric investigation of proton linkage by monitoring both the enthalpy and association constant of binding: application to the interaction of the Src SH2 domain with a high-affinity tyrosyl phosphopeptide.
  Biochemistry, 37, 15400-15407.  
9873628 J.M.Fu, and A.L.Castelhano (1998).
Design and synthesis of a pyridone-based phosphotyrosine mimetic.
  Bioorg Med Chem Lett, 8, 2813-2816.  
9685372 L.Tong, T.C.Warren, S.Lukas, J.Schembri-King, R.Betageri, J.R.Proudfoot, and S.Jakes (1998).
Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding.
  J Biol Chem, 273, 20238-20242.
PDB codes: 1bhf 1bhh
9817027 T.K.Sawyer (1998).
Src homology-2 domains: structure, mechanisms, and drug discovery.
  Biopolymers, 47, 243-261.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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