PDBsum entry 1awo

Kinase

PDB id: 1awo

Contents

Protein chain

57 a.a. *

* Residue conservation analysis

PDB id:

1awo

Name:

Kinase

Title:

The solution nmr structure of abl sh3 and its relationship to sh2 in the sh(32) construct, 20 structures

Structure:

Abl tyrosine kinase. Chain: a. Fragment: src-homology 3 (sh3) domain. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: expressed as gst fusions and cleaved

NMR struc:

20 models

Authors:

D.Cowburn

Key ref:

Y.Q.Gosser et al. (1995). The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct. Structure, 3, 1075-1086. PubMed id: 8590002 DOI: 10.1016/S0969-2126(01)00243-X

Date:

03-Oct-97 Release date: 28-Jan-98

Protein chain

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

Seq: 1130 a.a.

Struc: 57 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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(01)00243-X

Structure 3:1075-1086 (1995)

PubMed id: 8590002

The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct.

Y.Q.Gosser, J.Zheng, M.Overduin, B.J.Mayer, D.Cowburn.

ABSTRACT

BACKGROUND: The Src homology domains, SH3 and SH2, of Abl protein tyrosine kinase regulate enzymatic activity in vivo. Abl SH3 suppresses kinase activity, whereas Abl SH2 is required for the transforming activity of the activated form of Abl. We expect that the solution structures of Abl SH3, Abl SH2 and Abl SH(32) (a dual domain comprising SH3 and SH2 subdomains) will contribute to a structural basis for understanding the mechanism of the Abl 'regulatory apparatus'. RESULTS: We present the solution structure of the free Abl SH3 domain and a structural characterization of the Abl regulatory apparatus, the SH(32) dual domain. The solution structure of Abl SH3 was determined using multidimensional double resonance NMR spectroscopy. It consists of two antiparallel beta sheets packed orthogonally, an arrangement first shown in spectrin SH3. Compared with the crystal structure of the Abl SH3 complexed with a natural ligand, there is no significant difference in overall folding pattern. The structure of the Abl SH(32) dual domain was characterized by NMR spectroscopy using the 1H and 15N resonance assignment of Abl SH3 and Abl SH2. On the basis of the high degree of similarity in chemical shifts and hydrogen/deuterium exchange pattern for the individual domains of SH3 and SH2 compared with those of the SH(32) dual domain, a structural model of the Abl SH(32) regulatory apparatus is suggested. This model is in good agreement with the ligand-binding characteristics of Abl SH3, SH2 and SH(32). The binding constants for isolated SH3 and SH2 domains when binding to natural ligands, measured by intrinsic fluorescence quenching, do not differ significantly from the constants of these domains within SH(32). CONCLUSION: The solution structures of free Abl SH3 and Abl SH2, and the structural model of Abl SH(32), provide information about the overall topology of these modular domains. The structural model of Abl SH(32), a monomer, consists of the SH3 and SH2 domains connected by a flexible linker. Sites of ligand binding for the two subdomains are independent.

Selected figure(s)

Figure 2.
Figure 2. Sketch of the antiparallel β sheets, S1 and S2, in the Abl-SH3 solution structure. The observed long-range NOEs between strands are indicated by solid lines. Hydrogen bonds from slowly exchanging amides, supported by interstrand NOEs, are indicated by dashed lines. Figure 2. Sketch of the antiparallel β sheets, S1 and S2, in the Abl-SH3 solution structure. The observed long-range NOEs between strands are indicated by solid lines. Hydrogen bonds from slowly exchanging amides, supported by interstrand NOEs, are indicated by dashed lines.

Figure 9.
Figure 9. Sequences of Abl SH3, SH2 and SH(32) [1 and 34]. The elements of secondary structure are labeled as for the individual SH3 and SH2 domains. Loops and turns are not labeled. The residues in the linker region are indicated with bold green letters. Residues in lower case result from the expression system used. Figure 9. Sequences of Abl SH3, SH2 and SH(32) [[3]1 and [4]34]. The elements of secondary structure are labeled as for the individual SH3 and SH2 domains. Loops and turns are not labeled. The residues in the linker region are indicated with bold green letters. Residues in lower case result from the expression system used.

The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1075-1086) copyright 1995.

Figures were selected by an automated process.