EVOLUTIONARY DYNAMICS OF PROLIDASE SUBSTRATE SPECIFICITY ACROSS BIOLOGICAL KINGDOMS: A COMPUTATIONAL STRUCTURAL AND DOCKING ANALYSIS

Prolidase is a metalloprotease which functions primarily by catalysing the hydrolysis of Xaa-Proline (Xaa:any hydrophobic amino acid) and Xaa-Hydroxyproline(Hyp) dipeptides. This enzyme is ubiquitously present across the three biological domains, spanning all kingdoms of life. In the context of prokaryotic organisms, there has been a hypothesis suggesting that prolidase plays a role in nutrient acquisition and functions as a defence mechanism against toxins. However, the precise physiological function of prolidase in unicellular organisms remains yet to be definitively determined. Human prolidase is known to be involved in terminal steps of collagen metabolism. The present investigation was carried for in-silico evaluation of substrate specificity of Prolidase in selected representatives across genera of living systems. The study involved phylogenetic analysis, molecular modelling, structural analysis followed by molecular docking of Prolidase enzyme across genera of biological systems. Literature reports suggest that Glycine-Proline dipeptide is the preferred substrate for Prolidase. We compared the binding efficiency of three ligands viz. Glycine-Proline, Alanine-Proline and Methionine-Proline against Prolidase enzyme from different genera. Molecular docking results revealed in humans the substrate Alanine-Proline and Glycine-Proline had more or less comparable binding energies. Also, it was observed that as we move along the hierarchal system of classification the prolidase of most of the higher organisms were seen to prefer Methionine-Proline as substrate rather than Glycine-Proline. This data may provide a platform to discover role of prolidase in variety of organisms depending upon their binding specificity towards different substrates .