Philogenetic Analysis of ADAMTS-4 and ADAMTS-5 Structures

Abstract

ADAMTS-4 and -5 are aggrecanases that are involved in the development of osteoarthrosis by breaking aggrecan at various binding sites, of which cleavage in the Glu373-Ala374 bond plays the most important role in pathogenesis. Therefore, studying them is an urgent task to this day. Now, the structural features of these enzymes have already been studied, however, the influence of evolutionary development on their functions and enzymatic activity is not quite clear. In the framework of this research in silico studies have been conducted. They consist in the construction of phylogenetic trees by the maximum likelihood method in MEGA X program, the establishment of changes in the structures that occurred during evolution, and their possible effect on enzymatic activity. In addition, the organism most suitable for experimental studies has been determined. In this research, to analyze evolutionary changes, we have studied the sequences of organisms from different families: Salmon, Guinea fowl, Frog, Python, Rabbit, Leopard, Gorilla, Man. The lengths of these sequences are approximately equal; when aligning, the structures do not differ much. When studying the trees constructed from these sequences, it has been found that their structure is quite different only at the beginning, in the area of the signal surface and prodomain, while the rest of the changes are insignificant. The authors have also carried out the analysis of phylogenetic trees to determine an organism that is most like the human structure and therefore most suitable for in vivo studies. The following structures have been investigated: Bull, Camel, Pig, Donkey, Rabbit, Rat, Mouse, and Man. The rabbit has the most similar structure and therefore is more suitable for experimental studies.