Bioinformatics of thymidine metabolism in Trypanosoma evansi: exploring nucleoside deoxyribosyltransferase (NDRT) as a drug target.

Kandeel M

doi:10.47665/tb.38.3.071

Abstract

Trypanosoma evansi, the causative agent of surra or camel trypanosomiasis, is characterized by the widest geographic distribution and host range among the known trypanosomes. Its zoonotic importance and increasing evidence of drug resistance necessitate the discovery of new drug targets. The drug discovery process entails finding an exploitable difference between the host and the parasite. In this study, the thymidine metabolic pathways in camel and T. evansi were compared by analyzing their metabolic maps, protein sequences, domain and motif contents, phylogenetic relationships, and 3D structure models. The two organisms were revealed to recycle thymidine differently: performed by thymidine phosphorylase in camels (Camelus genus), this role in T. evansi was associated with nucleoside deoxyribosyltransferase (NDRT), a unique trypanosomal enzyme absent in camels. Thymidine in T. evansi seems to be governed by thymine through NDRT, whereas in camels, thymidine can be produced from thymidylate via 5'-nucleotidase. As a result, NDRT may be a promising drug target against T. evansi.

Highlights

Decoding camel (Camelus genus) genome sequences (Jirimutu et al, 2012) will accelerate drug discovery studies against camel pathogens
We plotted the pathway of thymidine metabolism in the two organisms, providing bioinformatics evidence of unique differences between camels and T. evansi that could be exploited for future drug discovery processes
Retrieval of protein sequences The NCBI protein database was used to obtain the sequences of camel enzymes, and the T. evansi protein sequences were retrieved from the Kinetoplastom genome project

Summary

Introduction

Decoding camel (Camelus genus) genome sequences (Jirimutu et al, 2012) will accelerate drug discovery studies against camel pathogens. One specific line of inquiry is investigating pyrimidine metabolic pathways, and finding unique differences in structure, function, sequence, or phylogeny associated with these pathways could contribute to identifying new drug targets. KEGG maps have been used (Ogata et al, 1998; Kanehisa et al, 2007; Kanehisa et al, 2016) to compare the enzymes involved in thymidine metabolism pathways in camels and T. evansi. Comprehensive bioinformatic tools were used to investigate enzyme sequences in camels and T. evansi and compare their domains and motif content, searching for similar proteins and identifying their phylogenetic relationships. We plotted the pathway of thymidine metabolism in the two organisms, providing bioinformatics evidence of unique differences between camels and T. evansi that could be exploited for future drug discovery processes

Methods

Results

Conclusion