PDBsum entry 1jqh

Transferase

PDB id: 1jqh

Contents

Protein chains

291 a.a. *

Ligands

SO4 ×3

ANP ×3

Metals

_MG

Waters ×252

* Residue conservation analysis

PDB id:

1jqh

Name:

Transferase

Title:

Igf-1 receptor kinase domain

Structure:

Igf-1 receptor kinase. Chain: a, b, c. Fragment: kinase domain. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Biol. unit:

Trimer (from PQS)

Resolution:

2.10Å R-factor: 0.195 R-free: 0.219

Authors:

A.Pautsch,A.Zoephel,H.Ahorn,W.Spevak,R.Hauptmann,H.Nar

Key ref:

A.Pautsch et al. (2001). Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation. Structure, 9, 955-965. PubMed id: 11591350 DOI: 10.1016/S0969-2126(01)00655-4

Date:

07-Aug-01 Release date: 19-Apr-02

Protein chains

P08069  (IGF1R_HUMAN) -  Insulin-like growth factor 1 receptor from Homo sapiens

Seq: 1367 a.a.

Struc: 291 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + H(+)

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

Added reference

DOI no: 10.1016/S0969-2126(01)00655-4

Structure 9:955-965 (2001)

PubMed id: 11591350

Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation.

A.Pautsch, A.Zoephel, H.Ahorn, W.Spevak, R.Hauptmann, H.Nar.

ABSTRACT

BACKGROUND: The insulin-like growth-factor-1 (IGF-1) receptor, which is widely expressed in cells that have undergone oncogenic transformation, is emerging as a novel target in cancer therapy. IGF-1-induced receptor activation results in autophosphorylation of cytoplasmic kinase domains and enhances their capability to phosphorylate downstream substrates. Structures of the homologous insulin receptor kinase (IRK) exist in an open, unphosphorylated form and a closed, trisphosphorylated form. RESULTS: We have determined the 2.1 A crystal structure of the IGF-1 receptor protein tyrosine kinase domain phosphorylated at two tyrosine residues within the activation loop (IGF-1RK2P) and bound to an ATP analog. The ligand is not in a conformation compatible with phosphoryl transfer, and the activation loop is partially disordered. Compared to the homologous insulin receptor kinase, IGF-1RK2P is trapped in a half-closed, previously unobserved conformation. Observed domain movements can be dissected into two orthogonal rotational components. CONCLUSIONS: Conformational changes upon kinase activation are triggered by the degree of phosphorylation and are crucially dependent on the conformation of the proximal end of the kinase activation loop. This IGF-1RK structure will provide a molecular basis for the design of selective antioncogenic therapeutic agents.

Selected figure(s)

Figure 5.
Figure 5. Active Center and AMP-PNP Binding(a) AMP-PNP interactions in the active site of IGF-1RK2P. The protein is shown as a backbone representation (the glycine-rich loop is orange and transparent, the hinge region is magenta, the catalytic loop is green, and the activation loop is light yellow). Atoms are color coded by type: carbon is yellow, oxygen is red, nitrogen is blue, sulfur is green, phosphorous is purple, and Mg2+ is black. Water molecules are blue-green spheres.

The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 955-965) copyright 2001.

Figure was selected by an automated process.