Abstract
The serine protease inhibitors (serpins) are a family of proteins that function to control the action of serine proteases in many diverse physiological processes. The functional region or reactive centre of these inhibitors is near the C-terminal end and is an exposed site that acts as a bait for the appropriate serine protease to recognize and covalently bind. The specificity of the inhibitor is determined, at least in part, by a single amino acid that resides in this region at the P1 position1. We show here that following a gene duplication event the reactive centres of three related rodent protease inhibitors have diverged from each other at unprecedented rates. This has resulted in proteins with different predicted specificities and we postulate that these changes were fixed by positive darwinian selection and that the most likely selective forces are extrinsic proteases, namely those used by parasites to facilitate their spread throughout the host.
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Hill, R., Hastie, N. Accelerated evolution in the reactive centre regions of serine protease inhibitors. Nature 326, 96–99 (1987). https://doi.org/10.1038/326096a0
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DOI: https://doi.org/10.1038/326096a0
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