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Chemistry and Biology of Serpins pp 207–222Cite as

Dysfunctional Variants and the Structural Biology of the Serpins

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 425))

Abstract

The development of our knowledge of the serpins illustrates the advantages of considering a protein superfamily as a whole. The serpins have all retained a common tertiary structure despite the individual evolution of diverse functions; for example, the homology of the plasma protease inhibitor α1-antitrypsin is closer to that of corticosteroid binding globulin than is the homology of the two heparin-binding plasma inhibitors — antithrombin and heparin cofactor II — one to another. This retention of a well conserved structure necessarily requires the retention of strong homologies in primary and secondary structures in all the members of the family, across functions as well as species. For this reason, from the beginning, the study of the serpins has been a collective process with our understanding of the function of each member being greatly strengthened by parallel studies of other serpins. This has been particularly true of the lessons learnt from the human dysfunctional variants; one by one they have provided clues as to the normal function in individual members but when considered together with structural studies, in terms of the family as a whole, they have opened our understanding to a degree that far surpasses the contribution of more conventional approaches.

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Authors and Affiliations

  1. Department of Haematology, University of Cambridge MRC Centre, Hills Road, Cambridge, CB2 2QH, England

    Robin Carrell, David Lomas, Penelope Stein & James Whisstock

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  1. Robin Carrell
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  2. David Lomas
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  3. Penelope Stein
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  4. James Whisstock
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Editor information

Editors and Affiliations

  1. University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

    Frank C. Church

  2. University of California, Irvine, California, USA

    Dennis D. Cunningham

  3. Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan, USA

    David Ginsburg

  4. Duke University and Durham VA Medical Centers, Durham, North Carolina, USA

    Maureane Hoffman

  5. Late of Monash University, Clayton, Victoria, Australia

    Stuart R. Stone

  6. Washington University School of Medicine, St. Louis, Missouri, USA

    Douglas M. Tollefsen

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Carrell, R., Lomas, D., Stein, P., Whisstock, J. (1997). Dysfunctional Variants and the Structural Biology of the Serpins. In: Church, F.C., Cunningham, D.D., Ginsburg, D., Hoffman, M., Stone, S.R., Tollefsen, D.M. (eds) Chemistry and Biology of Serpins. Advances in Experimental Medicine and Biology, vol 425. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5391-5_20

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  • DOI: https://doi.org/10.1007/978-1-4615-5391-5_20

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