title: Structure of a protein in a kinetic trap.
abstract: We have determined the structure of a metastable disulphide isomer of human insulin. Although not observed for proinsulin folding or insulin-chain recombination, the isomer retains ordered secondary structure and a compact hydrophobic core. Comparison with native insulin reveals a global rearrangement in the orientation of A- and B-chains. One face of the protein's surface is nevertheless in common between native and non-native structures. This face contains receptor-binding determinants, rationalizing the partial biological activity of the isomer. Structures of native and non-native disulphide isomers also define alternative three-dimensional templates. Threading of insulin-like sequences provide an experimental realization of the inverse protein-folding problem.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637-5419, USA.
authors.forename: Q X
authors.initials: QX
authors.lastname: Hua
authors.forename: S N
authors.initials: SN
authors.lastname: Gozani
authors.forename: R E
authors.initials: RE
authors.lastname: Chance
authors.forename: J A
authors.initials: JA
authors.lastname: Hoffmann
authors.forename: B H
authors.initials: BH
authors.lastname: Frank
authors.forename: M A
authors.initials: MA
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011972:Receptor, Insulin / Q000378:metabolism; D013698:Templates, Genetic; D013816:Thermodynamics
chemical_list: D007328:Insulin; D011384:Proinsulin; D011972:Receptor, Insulin