PDBsum entry 1k1f

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
(+ 1 more) 67 a.a.
63 a.a.
Waters ×420
PDB id:
Name: Transferase
Title: Structure of the bcr-abl oncoprotein oligomerization domain
Structure: Breakpoint cluster region protein. Chain: a, b, c, d, e, f, g, h. Fragment: bcr1-72. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PQS)
2.20Å     R-factor:   0.262     R-free:   0.295
Authors: X.Zhao,S.Ghaffari,H.Lodish,V.N.Malashkevich,P.S.Kim
Key ref:
X.Zhao et al. (2002). Structure of the Bcr-Abl oncoprotein oligomerization domain. Nat Struct Biol, 9, 117-120. PubMed id: 11780146 DOI: 10.1038/nsb747
25-Sep-01     Release date:   06-Feb-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P11274  (BCR_HUMAN) -  Breakpoint cluster region protein
1271 a.a.
67 a.a.*
Protein chain
Pfam   ArchSchema ?
P11274  (BCR_HUMAN) -  Breakpoint cluster region protein
1271 a.a.
63 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H: E.C.  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   2 terms 
  Biochemical function     GTPase activator activity     2 terms  


DOI no: 10.1038/nsb747 Nat Struct Biol 9:117-120 (2002)
PubMed id: 11780146  
Structure of the Bcr-Abl oncoprotein oligomerization domain.
X.Zhao, S.Ghaffari, H.Lodish, V.N.Malashkevich, P.S.Kim.
The Bcr-Abl oncoprotein is responsible for a wide range of human leukemias, including most cases of Philadelphia chromosome-positive chronic myelogenous leukemia. Oligomerization of Bcr-Abl is essential for oncogenicity. We determined the crystal structure of the N-terminal oligomerization domain of Bcr-Abl (residues 1-72 or Bcr1-72) and found a novel mode of oligomer formation. Two N-shaped monomers dimerize by swapping N-terminal helices and by forming an antiparallel coiled coil between C-terminal helices. Two dimers then stack onto each other to form a tetramer. The Bcr1-72 structure provides a basis for the design of inhibitors of Bcr-Abl transforming activity by disrupting Bcr-Abl oligomerization.
  Selected figure(s)  
Figure 3.
Figure 3. Packing of Bcr[1−72] tetramers with two orthogonal views. The tetramer has an approximate 222-point symmetry, with three two-fold rotation axes intersecting near Leu 45. The four monomers are colored in yellow, blue, dark purple and light purple. a, Top view looking down the flat surface of helix bundles in dimers. b, Side view showing dimer−dimer stacking.
Figure 4.
Figure 4. Dimer−dimer interface. Upon the association of two dimers, 3,400 Å^2 of the solvent-accessible surface is buried. There are two views of the surface electrostatic potential of one dimer, with the other dimer displayed as a ribbon. Basic regions on the surface are blue, and acidic regions are red. The side chains of the residues involved in dimer−dimer interactions are shown. a, Front view of the highly hydrophobic surface involved in the association with another dimer. b, Back view showing the highly hydrophilic surface that is solvent exposed.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 117-120) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21347248 M.Preyer, P.Vigneri, and J.Y.Wang (2011).
Interplay between Kinase Domain Autophosphorylation and F-Actin Binding Domain in Regulating Imatinib Sensitivity and Nuclear Import of BCR-ABL.
  PLoS One, 6, e17020.  
21310073 S.J.Yi, J.Groffen, and N.Heisterkamp (2011).
Bcr is a substrate for Transglutaminase 2 cross-linking activity.
  BMC Biochem, 12, 8.  
21049125 V.N.Uversky (2011).
Multitude of binding modes attainable by intrinsically disordered proteins: a portrait gallery of disorder-based complexes.
  Chem Soc Rev, 40, 1623-1634.  
20430957 C.Wichmann, Y.Becker, L.Chen-Wichmann, V.Vogel, A.Vojtkova, J.Herglotz, S.Moore, J.Koch, J.Lausen, W.Mäntele, H.Gohlke, and M.Grez (2010).
Dimer-tetramer transition controls RUNX1/ETO leukemogenic activity.
  Blood, 116, 603-613.  
20841568 J.Colicelli (2010).
ABL tyrosine kinases: evolution of function, regulation, and specificity.
  Sci Signal, 3, re6.  
18827185 A.Quintás-Cardama, and J.Cortes (2009).
Molecular biology of bcr-abl1-positive chronic myeloid leukemia.
  Blood, 113, 1619-1630.  
19576252 A.S.Dixon, M.Kakar, K.M.Schneider, J.E.Constance, B.C.Paullin, and C.S.Lim (2009).
Controlling subcellular localization to alter function: Sending oncogenic Bcr-Abl to the nucleus causes apoptosis.
  J Control Release, 140, 245-249.  
19888473 H.Hegyi, L.Buday, and P.Tompa (2009).
Intrinsic structural disorder confers cellular viability on oncogenic fusion proteins.
  PLoS Comput Biol, 5, e1000552.  
19208803 Q.Y.Zhang, J.H.Mao, P.Liu, Q.H.Huang, J.Lu, Y.Y.Xie, L.Weng, Y.Zhang, Q.Chen, S.J.Chen, and Z.Chen (2009).
A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia.
  Proc Natl Acad Sci U S A, 106, 3378-3383.  
18354488 D.W.Sherbenou, O.Hantschel, L.Turaga, I.Kaupe, S.Willis, T.Bumm, R.D.Press, G.Superti-Furga, B.J.Druker, and M.W.Deininger (2008).
Characterization of BCR-ABL deletion mutants from patients with chronic myeloid leukemia.
  Leukemia, 22, 1184-1190.  
18366061 T.Beissert, A.Hundertmark, V.Kaburova, L.Travaglini, A.A.Mian, C.Nervi, and M.Ruthardt (2008).
Targeting of the N-terminal coiled coil oligomerization interface by a helix-2 peptide inhibits unmutated and imatinib-resistant BCR/ABL.
  Int J Cancer, 122, 2744-2752.  
17671641 D.W.Sherbenou, and B.J.Druker (2007).
Applying the discovery of the Philadelphia chromosome.
  J Clin Invest, 117, 2067-2074.  
16640460 N.M.Levinson, O.Kuchment, K.Shen, M.A.Young, M.Koldobskiy, M.Karplus, P.A.Cole, and J.Kuriyan (2006).
A Src-like inactive conformation in the abl tyrosine kinase domain.
  PLoS Biol, 4, e144.
PDB codes: 2g1t 2g2f 2g2h 2g2i
16283145 D.C.Fry, and L.T.Vassilev (2005).
Targeting protein-protein interactions for cancer therapy.
  J Mol Med, 83, 955-963.  
16161117 L.P.Silva, R.B.Azevedo, P.C.Morais, M.M.Ventura, and S.M.Freitas (2005).
Oligomerization states of Bowman-Birk inhibitor by atomic force microscopy and computational approaches.
  Proteins, 61, 642-648.  
15143160 C.E.Tognon, C.D.Mackereth, A.M.Somasiri, L.P.McIntosh, and P.H.Sorensen (2004).
Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block polymerization and transformation activity.
  Mol Cell Biol, 24, 4636-4650.  
12887890 K.M.Smith, R.Yacobi, and R.A.Van Etten (2003).
Autoinhibition of Bcr-Abl through its SH3 domain.
  Mol Cell, 12, 27-37.  
12086882 C.L.Sawyers (2002).
Disabling Abl-perspectives on Abl kinase regulation and cancer therapeutics.
  Cancer Cell, 1, 13-15.  
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.