Abstract.
A serine protease inhibitor of the Kunitz-STI (soybean trypsin inhibitor) family, isolated from the legume seeds of winged bean, was found to inhibit chymotrypsin at a 1:2 stoichiometric ratio. When the structure was determined in our laboratory, it was found to form a characteristic β-trefoil fold, which is also seen in other proteins from distant families and sources. The folding organization divides the protein into three approximately equal subdomains related by a pseudo-threefold axis of symmetry passing parallel to the barrel axis of the trefoil. Following the now established idea that the present-day genes originated from ancestral minigenes through evolution, the origin of the proteins having this β-trefoil organization is scrutinized using its subdomain motif as the search probe. The results, based mainly on structural analyses, indicate the independent existence of such a motif, mimicking the unknown ancestral protein(s) that might have been distributed in nature, not only by gene duplication, but also by insertion and permutation in other folds. The understanding led to a hypothesis for the possible origin of the Kunitz-STI family. On the basis of this model of evolution, structurally hypervariable regions were located on the protein where mutations could be designed and a broad range of engineering of the protein's activity could be conceived.
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Received: 20 January 1999 / Accepted: 6 October 1999
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Mukhopadhyay, D. The Molecular Evolutionary History of a Winged Bean α-Chymotrypsin Inhibitor and Modeling of Its Mutations Through Structural Analyses. J Mol Evol 50, 214–223 (2000). https://doi.org/10.1007/s002399910024
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DOI: https://doi.org/10.1007/s002399910024