Identification of accelerated evolution in the metalloproteinase domain of snake venom metalloproteinase sequences (SVMPs) through comparative analysis

Abstract

Computational protein sequence analysis is one of the most important tools used for understanding the evolution of closely related proteins sequences including snake venom metalloproteinase sequences (SVMPs) which give valuable information regarding genetic variations. The fundamental objective of the present study is to screen the evolution distributed in metalloproteinase domain regions of protein sequences among different SVMPs in snake species which are involved in a range of pathological disorders such as arthritis, atherosclerosis, liver fibrosis, cardiovascular, cancer, liver and neurodegenerative disorders. In fact, SVMPS are responsible for hemorrhage and may also interfere with the hemostatic system. A comparative characterization of the metalloproteinase sequences has been carried out to analyze their multiple sequence alignment, phylogenic tree, homology, physicochemical, secondary structural and functional properties. DNAMAN software was used for multiple sequence alignment, phylogenic tree and homology and Expasy's Prot-param server was used for amino acid composition, physico-chemical and functional characterization of these SVMPs sequences. Studies of secondary structure of these SVMPs were carried out by computational program. Based on the observed patterns of occurrence of atypical features, we hypothesize that amino acids of metalloproteinase domain region (66.63% identity) of protein sequences are highly changeable; whereas, signal peptide region (93.98% identity) is the lowest changeable protein sequence and the remaining other three domains such as propeptide region (87.36% identity), desintegrin domain region (78.63% identity) and cysteine-rich domain region (75.70% identity) show moderate changeable protein sequence. SVMPs might be an accelerated evolution, which is a key player in causing diseases. From the data, it can be suggested that over -changed metalloproteinase domain regions in snake venom metalloproteinase might be responsible for the generation of functional variation of proteins expressed, which in turn may lead to different disorders in humans after snake bite. The results of this study would be an effective tool for the study of mutation, drugs resistance mechanisms and development of new drugs for different diseases.

Unraveling the Reaction Mechanism of Russell’s Viper Venom Factor X Activator: A Paradigm for the Reactivity of Zinc Metalloproteinases?

“…SVMP structures have a typical topology, consisting of six α-helices and five stranded β-sheets in the M domain where the zinc ion is localized. Besides, sequence comparison between the M domains of SVMPs reveals quite high identity values of around 66% . This chemical and stereochemical match, particularly at the active site region, allows us to hypothesize that many of the members of this family of enzymes share a common catalytic mechanism.…”

“…Besides, sequence comparison between the M domains of SVMPs reveals quite high identity values of around 66%. 65 This chemical and stereochemical match, particularly at the active site region, allows us to hypothesize that many of the members of this family of enzymes share a common catalytic mechanism. Therefore, our results concerning the intricacies of the RVV-X mechanism might be extrapolated to many other members of this vast family.…”