PDBsum entry 1k1f

Transferase

PDB id: 1k1f

Contents

Protein chains

(+ 1 more) 67 a.a.

63 a.a.

Waters ×420

PDB id:

1k1f

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)

Resolution:

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

Date:

25-Sep-01 Release date: 06-Feb-02

Protein chains

P11274  (BCR_HUMAN) -  Breakpoint cluster region protein from Homo sapiens

Seq: 1271 a.a.

Struc: 67 a.a.*

Protein chain

P11274  (BCR_HUMAN) -  Breakpoint cluster region protein from Homo sapiens

Seq: 1271 a.a.

Struc: 63 a.a.*

* 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.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

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.

ABSTRACT

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.