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PDBsum entry 2e2b
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protein ligands Protein-protein interface(s) links
Transferase PDB id
2e2b

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
270 a.a. *
Ligands
406 ×2
Waters ×135
* Residue conservation analysis
PDB id:
2e2b
Name: Transferase
Title: Crystal structure of thE C-abl kinase domain in complex with inno-406
Structure: Proto-oncogene tyrosine-protein kinase abl1. Chain: a, b. Fragment: kinase domain. Synonym: p150, c-abl, abelson murine leukemia viral oncogene homolog 1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.20Å     R-factor:   0.236     R-free:   0.270
Authors: T.Horio,T.Hamasaki,T.Wakayama,K.Takagaki,T.Ohgi
Key ref: T.Horio et al. (2007). Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives. Bioorg Med Chem Lett, 17, 2712-2717. PubMed id: 17376680 DOI: 10.1016/j.bmcl.2007.03.002
Date:
10-Nov-06     Release date:   22-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00519  (ABL1_HUMAN) -  Tyrosine-protein kinase ABL1 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1130 a.a.
270 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 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: 10.1016/j.bmcl.2007.03.002 Bioorg Med Chem Lett 17:2712-2717 (2007)
PubMed id: 17376680  
 
 
Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives.
T.Horio, T.Hamasaki, T.Inoue, T.Wakayama, S.Itou, H.Naito, T.Asaki, H.Hayase, T.Niwa.
 
  ABSTRACT  
 
To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of the Abl/Lyn dual inhibitor INNO-406 (formerly known as NS-187) bound to human Abl. We found that this series of compounds interacted with both kinases in very similar ways, so that they can inhibit both kinases effectively.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19714578 S.Schenone, O.Bruno, M.Radi, and M.Botta (2011).
New insights into small-molecule inhibitors of Bcr-Abl.
  Med Res Rev, 31, 1.  
19890374 U.Rix, L.L.Remsing Rix, A.S.Terker, N.V.Fernbach, O.Hantschel, M.Planyavsky, F.P.Breitwieser, H.Herrmann, J.Colinge, K.L.Bennett, M.Augustin, J.H.Till, M.C.Heinrich, P.Valent, and G.Superti-Furga (2010).
A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells.
  Leukemia, 24, 44-50.  
19053777 I.Kufareva, and R.Abagyan (2008).
Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states.
  J Med Chem, 51, 7921-7932.  
18759691 R.Tanaka, and S.Kimura (2008).
Abl tyrosine kinase inhibitors for overriding Bcr-Abl/T315I: from the second to third generation.
  Expert Rev Anticancer Ther, 8, 1387-1398.  
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.

 

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