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Structure of a protein in a kinetic trap

Nature Structural Biology volume 2, pages 129–138 (1995)Cite this article

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.

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Author information

Authors and Affiliations

  1. Center for Biomolecular Structure and Function and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, 60637-5419, USA

    Qing-Xin Hua

  2. Harvard-MIT Program in Health Sciences and Technology, Boston, Massachusetts, 02115, USA

    Shai N. Gozani

  3. Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana, 46285, USA

    Ronald E. Chance, James A. Hoffmann & Bruce H. Frank

  4. Department of Chemistry, University of Chicago, Chicago, Illinois, 60637, USA

    Michael A. Weiss

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  1. Qing-Xin Hua
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  2. Shai N. Gozani
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  4. James A. Hoffmann
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  5. Bruce H. Frank
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  6. Michael A. Weiss
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Hua, QX., Gozani, S., Chance, R. et al. Structure of a protein in a kinetic trap. Nat Struct Mol Biol 2, 129–138 (1995). https://doi.org/10.1038/nsb0295-129

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