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Structure of a specific acyl-enzyme complex formed between β-casomorphin-7 and porcine pancreatic elastase

Nature Structural Biology volume 4, pages 456–462 (1997)Cite this article

Abstract

Mass spectrometric screening reveals that an unmodified natural heptapeptide—human β-casomorphin-7, an internal sequence of human β-casein that possesses opioid-like activity—reacts with porcine pancreatic elastase to form an unusually stable acyl-enzyme complex at low pH. X-ray crystallographic analysis (to 1.9 Å resolution) at pH 5 shows continuous electron density linking the C-terminal isoleucine of β-casomorphin-7 to Ser 195 through an ester bond. The structure reveals a well defined water molecule (Wat 317), equidistant between the carbon of the ester carbonyl and Nε2 of His 57. Deprotonation of Wat 317 will produce a hydroxide ion positioned to attack the ester carbonyl through the favoured Bürgi-Dunitz trajectory.

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Authors and Affiliations

  1. The Oxford Centre for Molecular Sciences, South Parks Road, Oxford, 0X1 3QY, UK

    Rupert C. Wilmouth, Ian J. Clifton, Carol V. Robinson, Peter L. Roach, Nicholas J. Westwood, Janos Hajdu & Christopher J. Schofield

  2. The Dyson Perrins Laboratory, South Parks Road, Oxford, 0X1 3QY, UK

    Rupert C. Wilmouth, Peter L. Roach, Robin T. Aplin & Christopher J. Schofield

  3. Laboratory of Molecular Biophysics, South Parks Road, Oxford, 0X1 3QU, UK

    Ian J. Clifton & Janos Hajdu

  4. Department of Biochemistry, Uppsala University, Box 576, S-751,23, Uppsala, Sweden

    Janos Hajdu

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Wilmouth, R., Clifton, I., Robinson, C. et al. Structure of a specific acyl-enzyme complex formed between β-casomorphin-7 and porcine pancreatic elastase. Nat Struct Mol Biol 4, 456–462 (1997). https://doi.org/10.1038/nsb0697-456

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