Structure of apo, unactivated insulin-like growth factor-1 receptor kinase at 1.5 A resolution

Acta Crystallogr D Biol Crystallogr. 2003 Oct;59(Pt 10):1725-30. doi: 10.1107/s0907444903015415. Epub 2003 Sep 19.


The crystal structure of the wild-type unactivated kinase domain (IGFRK-0P) of insulin-like growth factor-1 receptor has been reported previously at 2.7 A resolution [Munshi et al. (2002), J. Biol. Chem. 277, 38797-38802]. In order to obtain a high-resolution structure, a number of variants of IGFRK-0P were prepared and screened for crystallization. A double mutant with E1067A and E1069A substitutions within the kinase-insert region resulted in crystals that diffracted to 1.5 A resolution. Overall, the structure of the mutant IGFRK-0P is similar to that of the wild-type IGFRK-0P structure, with the exception of the previously disordered kinase-insert region in the wild type having become fixed. In addition, amino-acid residues 947-952 at the N-terminus are well defined in the mutant structure. The monomeric protein structure is folded into two lobes connected by a hinge region, with the catalytic center situated at the interface of the two lobes. Two molecules of IGFRK-0P in the asymmetric unit are associated as a dimer and two different types of dimers with their ATP-binding clefts either facing towards or away from each other are observed. The current refined model consists of a dimer and 635 water molecules.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Apoproteins / chemistry*
  • Apoproteins / genetics
  • Binding Sites
  • Cells, Cultured
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • Insecta / enzymology
  • Models, Molecular
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptor, IGF Type 1 / chemistry*
  • Receptor, IGF Type 1 / genetics
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics


  • Apoproteins
  • Recombinant Proteins
  • Receptor, IGF Type 1