PDBsum entry 2z8c

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protein ligands links
Transferase PDB id
Jmol PyMol
Protein chain
300 a.a. *
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Phosphorylated insulin receptor tyrosine kinase in complex with (4-{[5-carbamoyl-4-(3-methylanilino)pyrimidin-2- yl]amino}phenyl)acetic acid
Structure: Insulin receptor. Chain: a. Fragment: tyrosine kinase domain. Synonym: ir, cd220 antigen. Engineered: yes. Mutation: yes. 6-mer peptide from insulin receptor substrate 1. Chain: b. Synonym: irs-1.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: insr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Gene: irs1.
3.25Å     R-factor:   0.217     R-free:   0.292
Authors: N.Katayama,H.Kurihara
Key ref:
N.Katayama et al. (2008). Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors. Proteins, 73, 795-801. PubMed id: 18767165 DOI: 10.1002/prot.22207
05-Sep-07     Release date:   12-Aug-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P06213  (INSR_HUMAN) -  Insulin receptor
1382 a.a.
300 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Bound ligand (Het Group name = TYR)
matches with 70.00% similarity
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     protein kinase activity     2 terms  


DOI no: 10.1002/prot.22207 Proteins 73:795-801 (2008)
PubMed id: 18767165  
Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors.
N.Katayama, M.Orita, T.Yamaguchi, H.Hisamichi, S.Kuromitsu, H.Kurihara, H.Sakashita, Y.Matsumoto, S.Fujita, T.Niimi.
In this article, we report crystal structures for inhibitor-kinase complexes in which the inhibitor has different binding orientations and hydrogen-bonding patterns with extracellular-signal regulated kinase 2 and insulin receptor tyrosine kinase. Our crystallographic studies, and sequence and structural analyses of 532 coordinates of kinases held in the Protein Data Bank, suggest that the length of the "specificity linker" described here is a key structural element of the hydrogen-bonding patterns between protein kinases and their inhibitors. Proteins 2008. (c) 2008 Wiley-Liss, Inc.
  Selected figure(s)  
Figure 1.
Figure 1. Schematics showing the binding mode of ligands to protein kinases. (a) ATP. (b) Purvalanol B in CDK2 (PDB code 1CKP). (c) NU2058 in CDK2 (PDB code 1E1V). Hydrogen bonds are indicated by broken lines.
Figure 5.
Figure 5. Key elements for the hydrogen-bonding pattern of an ATP-mimetic compound. The orientation of R3-O of the group A kinase is more favorable for that of the group B kinase because of the difference in the length of the specificity linker.
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 73, 795-801) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20306284 A.Del Rio, M.Sgobba, M.D.Parenti, G.Degliesposti, R.Forestiero, C.Percivalle, P.F.Conte, M.Freccero, and G.Rastelli (2010).
A computational workflow for the design of irreversible inhibitors of protein kinases.
  J Comput Aided Mol Des, 24, 183-194.  
19689374 K.Burkhard, S.Smith, R.Deshmukh, A.D.MacKerell, and P.Shapiro (2009).
Development of extracellular signal-regulated kinase inhibitors.
  Curr Top Med Chem, 9, 678-689.  
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