Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions.

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Vajdos FF, Ultsch M, Schaffer ML, Deshayes KD, Liu J, Skelton NJ, de Vos AM

Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions.

Biochemistry. 2001 Sep 18;40(37):11022-9.

PubMed ID

11551198 [ View in PubMed

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Abstract

Despite efforts spanning considerably more than a decade, a high-resolution view of the family of proteins known as insulin-like growth factors (IGFs) has remained elusive. IGF-1 consists of three helical segments which are connected by a 12-residue linker known as the C-region. NMR studies of members of this family reveal a dynamic structure with a topology resembling insulin but little structural definition in the C-region. We have crystallized IGF-1 in the presence of the detergent deoxy big CHAPS, and determined its structure at 1.8 A resolution by multiwavelength anomalous diffraction, exploiting the anomalous scattering of a single bromide ion and six of the seven sulfur atoms of IGF-1. The structure reveals a well-defined conformation for much of the C-region, which extends away from the core of IGF-1 and has residues known to be involved in receptor binding prominently displayed in a type II beta-turn. In the crystal, these residues form a dimer interface, but analytical ultracentrifugation experiments demonstrate that at physiological concentrations IGF-1 is monomeric. A single detergent molecule contacts residues known to be important for IGF-1 binding protein (IGFBP) interactions. Biophysical and biochemical data show that the detergent binds to IGF-1 specifically and blocks binding of IGFBP-1 and IGFBP-3.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
N,N-Bis(3-(D-gluconamido)propyl)deoxycholamide	Insulin-like growth factor I	Protein	Humans	Unknown	Not Available	Details