| Full text | |
| Author(s): Show less - |
Romanello, Larissa
[1]
;
Zeraik, Ana Eliza
[1]
;
Fernandes, Adriano de Freitas
[1]
;
Torini, Juliana Roberta
[1]
;
Bird, Louise E.
[2, 3]
;
Nettleship, Joanne E.
[2, 3]
;
Rada, Heather
[2, 3]
;
Reddivari, Yamini
[2, 3]
;
Owens, Ray J.
[2, 3]
;
Serrao, Vitor Hugo Balasco
[4]
;
DeMarco, Ricardo
[1]
;
Brandao-Neto, Jose
[5]
;
Pereira, Humberto D'Muniz
[1]
Total Authors: 13
|
| Affiliation: | [1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13563120 Sao Carlos, SP - Brazil
[2] Rutherford Appleton Lab, OPPF UK, Res Complex Harwell, Oxford OX11 0FA - England
[3] Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Headington OX2 7BN, Oxon - England
[4] Univ Toronto, Lab Med & Pathobiol, Toronto, ON M5S 1A8 - Canada
[5] Diamond Light Source, Harwell Sci & Innovat Campus, Didcot OX11 0DE, Oxon - England
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Molecular and Biochemical Parasitology; v. 229, p. 24-34, APR 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
Schistosoma mansoni, the parasite responsible for schistosomiasis, lacks the ``de novo{''} purine biosynthetic pathway and depends entirely on the purine salvage pathway for the supply of purines. Numerous reports o praziquantel resistance have been described, as well as stimulated efforts to develop new drugs against schis tosomiasis. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine salvage pathway. Here, we describe a crystallographic structure of the S. mansoni HPGRT-1 (SmHGPRT), complexed witl IMP at a resolution of 2.8 angstrom. Four substitutions were identified in the region of the active site between SmHGPRT 1 and human HGPRT. We also present data from RNA-Seq and WISH, suggesting that some isoforms of HGPR1 might be involved in the process related to sexual maturation and reproduction in worms; furthermore, it: enzymatic assays show that the isoform SmHGPRT-3 does not present the same catalytic efficiency as other isoforms. Finally, although other studies have previously suggested this enzyme as a potential antischistosoma chemotherapy target, the kinetics parameters reveal the impossibility to use SmHGPRT as an efficient the motherapeutic target. (AU) | |
| FAPESP's process: | 12/05532-8 - Structural and kinetic studies of adenosine kinase, hypoxanthine-guanine phosphoribosyltransferase, Adenilsuccinate Synthetase and Adenilsuccinato Lyase enzymes from Schistosoma mansoni |
| Grantee: | Larissa Romanello |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 12/14223-9 - Structural and kinetical studies of the enzymes involved in the purine metabolism in Schistosoma mansoni |
| Grantee: | Humberto D'Muniz Pereira |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/20715-4 - Studies of the correlation between septin dynamics and Ca2+ homeostasis in muscular cells from Schistosoma mansoni |
| Grantee: | Ana Eliza Zeraik |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 12/23730-1 - Characterization of macromolecular interactions of proteins involved in the selenocysteine synthesis from Escherichia coli |
| Grantee: | Vitor Hugo Balasco Serrão |
| Support Opportunities: | Scholarships in Brazil - Doctorate |