Structural aspects of the serpin reaction coordinate

Summary

The important physiological roles and unique folding properties of the 50+ known members of the serpin superfamily have inspired a decade of interest in their structural biology. X-ray crystal structures of reactive-loop cleaved serpins, as well as reactive-loop intact (although inactive) serpins illuminate the inherent plasticity of their β-sheet superstructures, and this plasticity is critical for serpin function. Recent X-ray crystal structures of α1-antichymotrypsin and antithrombin III in their active and partially active forms, respectively, reveal two contrasting serpin conformations which may correlate with native and protease-bound conformations of the serpin reactive loop. In this Perspective, we review the current state of serpin structural biology and highlight the structural inferences on the reaction coordinate of the inhibitory mechanism.

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Correspondence to David W. Christianson.

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Katz, D.S., Christianson, D.W. Structural aspects of the serpin reaction coordinate. Perspectives in Drug Discovery and Design 2, 459–474 (1995). https://doi.org/10.1007/BF02172038

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Key words

  • Serine protease
  • Enzyme inhibitor
  • Plasticity
  • Reactive loop
  • β-Sheet rearrangement