Abstract:
Cystatins, a superfamily of evolutionary related proteins are classified as housekeeping proteins
vital for the inhibition of Papain-like cysteine proteases. Over expression of cysteine proteases
have been related to the development of diseases. These facts result in the realization of
Cystatins importance as regulators of protease activity and their role in the body’s immune
system. The Cystatin C protein understudy was identified from a pre-established transcriptomic
database of D. rerio using the NCBI database and the NCBI-BLAST algorithm. Cystatin C
belongs to the Type 2 Cystatin family and is the most powerful cysteine protease inhibitor
effective against Papain like proteases. The research study aims to develop an economical insilico
based approach to analyze the structure and functionality of novel proteins with a
comprehensive revelation of their clinical significance. Therefore, we report on novel in-silico
tools to generate a model of the Cystatin C protein expressed by D. rerio, prove its functionality
through molecular docking techniques and discover its immune potential against diseases caused
by Cathepsin over expression through the use of gene-gene interaction mapping. Through the
computational procedure a 99.99% accurate protein structure was predicted through homology
modelling techniques followed by successful inhibition of Papain and mammalian Cathepsins B,
H, L1 and S with therapeutic potential present for diseases caused by Cathepsin B and L1
overexpression. Analysis of the Cathepsin inhibition zone revealed a common binding site on the
Cystatin C proteins’ surface amoung seven closely related amino acids. In conclusion D. rerio
produces a Cystatin C protein that can successfully act as a cysteine protease inhibitor in addition
to bearing valuable therapeutic potential. Further analysis is required to confirm its tissue
specific expression, modulation under pathogenic conditions.
