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Homology modelling of the catalytic domain of early mammalian protein C: evolution of structural features

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Abstract

By means of a novel cDNA-based strategy employing the maximum parsimony principle, we have previously deduced probable amino acid sequences for the catalytic domains of the early mammalian ancestors of each of the five extant vitamin K-dependent serine proteases of coagulation, and for their common ancestor from a still earlier stage of vertebrate evolution. In the present study, we employed one of these sequences to construct a molecular model of the catalytic domain of early mammalian protein C and to explore its functional architecture. Following the domain’s progression from the common ancestor of the vitamin K-dependent serine proteases toward extant human protein C, this novel application of homology modelling to a reconstructed amino acid sequence has allowed us to trace the evolution of structural features in a vital coagulation protein.

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Authors and Affiliations

  1. Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, London SW3 6LR, UK Tel.: +44 171 3518330 ext. 3633; Fax: +44 171 3518324, , , , , , GB

    A. I. Wacey

  2. Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, UK Tel.: +44 122 2744062; Fax: +44 1222 747603, , , , , , GB

    M. Krawczak & D. N. Cooper

  3. Haemostasis Research Group, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK, , , , , , GB

    G. Kemball-Cook

Authors
  1. A. I. Wacey
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  2. M. Krawczak
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  3. G. Kemball-Cook
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  4. D. N. Cooper
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Received: 23 May 1997 / Accepted: 23 July 1997

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Wacey, A., Krawczak, M., Kemball-Cook, G. et al. Homology modelling of the catalytic domain of early mammalian protein C: evolution of structural features. Hum Genet 101, 37–42 (1997). https://doi.org/10.1007/s004390050582

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  • DOI: https://doi.org/10.1007/s004390050582

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