PDBsum entry 2abl

Transferase

PDB id: 2abl

Contents

Protein chain

163 a.a. *

Waters ×40

* Residue conservation analysis

PDB id:

2abl

Name:

Transferase

Title:

Sh3-sh2 domain fragment of human bcr-abl tyrosine kinase

Structure:

Abl tyrosine kinase. Chain: a. Fragment: sh3-sh2 domain fragment. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Gene: abl sh3-sh2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.50Å R-factor: 0.183 R-free: 0.270

Authors:

H.-J.Nam,C.A.Frederick

Key ref:

H.J.Nam et al. (1996). Intramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism. Structure, 4, 1105-1114. PubMed id: 8805596 DOI: 10.1016/S0969-2126(96)00116-5

Date:

17-Nov-96 Release date: 04-Sep-97

Protein chain

P00519  (ABL1_HUMAN) -  Tyrosine-protein kinase ABL1 from Homo sapiens

Seq: 1130 a.a.

Struc: 163 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: 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/S0969-2126(96)00116-5

Structure 4:1105-1114 (1996)

PubMed id: 8805596

Intramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism.

H.J.Nam, W.G.Haser, T.M.Roberts, C.A.Frederick.

ABSTRACT

BACKGROUND. The Abl nonreceptor tyrosine kinase is implicated in a range of cellular processes and its transforming variants are involved in human leukemias. The N-terminal regulatory region of the Abl protein contains Src homology domains SH2 and SH3 which have been shown to be important for the regulation of its activity in vivo. These domains are often found together in the same protein and biochemical data suggest that the functions of one domain can be influenced by the other. RESULTS. We have determined the crystal structure of the Abl regulatory region containing the SH3 and SH2 domains. In general, the individual domains are very similar to those of previously solved structures, although the Abl SH2 domain contains a loop which is extended so that one side of the resulting phosphotyrosine-binding pocket is open. In our structure the protein exists as a monomer with no intermolecular contacts to which a biological function may be attributed. However, there is a significant intramolecular contact between a loop of the SH3 domain and the extended loop of the SH2 domain. This contact surface includes the SH2 loop segment that is responsible for binding the phosphate moiety of phosphotyrosine-containing proteins and is therefore critical for orienting peptide interactions. CONCLUSIONS. The crystal structure of the composite Abl SH3-SH2 domain provides the first indication of how SH2 and SH3 domains communicate with each other within the same molecule and why the presence of one directly influences the activity of the other. This is the first clear evidence that these two domains are in contact with each other. The results suggest that this direct interaction between the two domains may affect the ligand binding properties of the SH2 domain, thus providing an explanation for biochemical and functional data concerning the Bcr-Abl kinase.

Selected figure(s)

Figure 2.
Figure 2. Schematic diagram and surface structure of the Abl SH3–SH2 regulatory region. (a) Richardson diagram of the Abl SH3–SH2 protein showing the relative positions of the SH3 and SH2 domains in one molecule. The SH2 domain is at the top of the figure and the SH3 domain at the bottom. In the SH2 domain the β strands are shown in red and the α helices in green; in the SH3 domain the β strands are in yellow. The secondary structure elements are numbered according to the convention of Eck, et al. [31] with individual residues identified by their position within each element or connecting loop; this numbering is used throughout. (The figure was made with the program MOLSCRIPT [51].) (b) The molecular surface of the Abl SH3–SH2 structure. The surface is colored according to the local electrostatic potential, ranging from blue (the most positive region) to red (the most negative). The putative phosphotyrosine-binding pocket and a hydrophobic (pTyr + 3 pocket are indicated. Important residues for the ligand binding of the SH3 domain are also indicated. Figure 2. Schematic diagram and surface structure of the Abl SH3–SH2 regulatory region. (a) Richardson diagram of the Abl SH3–SH2 protein showing the relative positions of the SH3 and SH2 domains in one molecule. The SH2 domain is at the top of the figure and the SH3 domain at the bottom. In the SH2 domain the β strands are shown in red and the α helices in green; in the SH3 domain the β strands are in yellow. The secondary structure elements are numbered according to the convention of Eck, et al. [[3]31] with individual residues identified by their position within each element or connecting loop; this numbering is used throughout. (The figure was made with the program MOLSCRIPT [[4]51].) (b) The molecular surface of the Abl SH3–SH2 structure. The surface is colored according to the local electrostatic potential, ranging from blue (the most positive region) to red (the most negative). The putative phosphotyrosine-binding pocket and a hydrophobic (pTyr + 3 pocket are indicated. Important residues for the ligand binding of the SH3 domain are also indicated. (The figure was made using the program GRASP [[5]52].)

Figure 6.
Figure 6. Ramachandram plot of the refined structure. Glycine and non-glycine ψ, φ pairs are designated by triangles and squares, respectively. Disallowed, generously allowed, favorable and most favorable regions are indicated by progressively darker shading. Of all the residues, 89% are in the most favorable regions and none of the residues are in disallowed regions. Figure 6. Ramachandram plot of the refined structure. Glycine and non-glycine ψ, φ pairs are designated by triangles and squares, respectively. Disallowed, generously allowed, favorable and most favorable regions are indicated by progressively darker shading. Of all the residues, 89% are in the most favorable regions and none of the residues are in disallowed regions.

The above figures are reprinted by permission from Cell Press: Structure (1996, 4, 1105-1114) copyright 1996.

Figures were selected by an automated process.