Evolutionary Aspects of the Structural Convergence and Functional Diversification of Kunitz-Domain Inhibitors.

Journal of Molecular Evolution
Manasi Mishra

Abstract

Kunitz-type domains are ubiquitously found in natural systems as serine protease inhibitors or animal toxins in venomous animals. Kunitz motif is a cysteine-rich peptide chain of ~ 60 amino acid residues with alpha and beta fold, stabilized by three conserved disulfide bridges. An extensive dataset of amino acid variations is found on sequence analysis of various Kunitz peptides. Kunitz peptides show diverse biological activities like inhibition of proteases of other classes and/or adopting a new function of blocking or modulating the ion channels. Based on the amino acid residues at the functional site of various Kunitz-type inhibitors, it is inferred that this 'flexibility within the structural rigidity' is responsible for multiple biological activities. Accelerated evolution of functional sites in response to the co-evolving molecular targets of the hosts of venomous animals or parasites, gene sharing, and gene duplication have been discussed as the most likely mechanisms responsible for the functional heterogeneity of Kunitz-domain inhibitors.

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Citations

Aug 30, 2021·Toxicon : Official Journal of the International Society on Toxinology·Karoline SanchesRaymond S Norton

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