Evolutionary and compositional analysis of streptokinase including its interaction with plasminogen: An in silico approach

Abstract

Due to the accumulation of cholesterol in arterial wall, clot-forming cascade activated in the blood capillaries lead to conditions like myocardial ischemia and heart failure. These clots are dissolved by the enzyme streptokinase (SK), produced by Streptococcus sp., a normal flora in the human body. In the present study, codon-dependent evolution of twenty-three SK from Streptococcus sp. bacteria, isolated from distinct geographical origins were analyzed. Besides, domain variation, compositional analysis, effective number of codons (ENc) plot, codon adaptation index (CAI), and effect of polymorphism on SK interaction with its substrate plasminogen (Plg) were analyzed. Codon usage bias varied within a tiny range. Studies also reveal that AT ending codons are preferred over GC ending codons. Analyses of the other parameters reveal that the mutational pressure is one of the main factors to shape codon usage biasness. Interfacing and polar contact forming amino acid residues of SK with Plg is identical for all Streptococcus dysgalactiae but not for all Streptococcus pyogenes. Changes of those interfacing amino acid sites exhibit a substantial effect on polar interaction between SK and Plg. The present in silico studies are expected to shed further light to characterize and moreover, to understand the various contributing factors to influence SK adaptation that will be fulfilling to develop efficient thrombolytic therapeutics.