Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5’-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway

8Citations
Citations of this article
25Readers
Mendeley users who have this article in their library.

Abstract

Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S. mansoni and could be a promising target for anti-schistosoma therapies. Here, we present 13 SmMTAP structures from the wild type (WT), including three single and one double mutant, and generate a solid structural framework for structure description. These crystal structures of SmMTAP reveal that the active site contains three substitutions within and near the active site when compared to it mammalian counterpart, thus opening up the possibility of developing specific inhibitors to the parasite MTAP. The structural and kinetic data for 5 substrates reveal the structural basis for this interaction, providing substract for inteligent design of new compounds for block this enzyme activity.

References Powered by Scopus

Coot: Model-building tools for molecular graphics

25801Citations
N/AReaders
Get full text

XDS

13248Citations
N/AReaders
Get full text

Scaling and assessment of data quality

4055Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties

42Citations
N/AReaders
Get full text

Substrate spectra of nucleoside phosphorylases and their potential in the production of pharmaceutically active compounds

32Citations
N/AReaders
Get full text

Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets

24Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Torini, J. R., Brandão-Neto, J., DeMarco, R., & Pereira, H. D. M. (2016). Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5’-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway. PLoS Neglected Tropical Diseases, 10(12). https://doi.org/10.1371/journal.pntd.0005178

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 7

50%

Researcher 5

36%

Professor / Associate Prof. 2

14%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 5

36%

Chemistry 4

29%

Biochemistry, Genetics and Molecular Bi... 4

29%

Chemical Engineering 1

7%

Save time finding and organizing research with Mendeley

Sign up for free