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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The molecular structure of Schistosoma mansoni PNP isoform 2 provides insights into the nucleoside selectivity of PNPs

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Torini, Juliana Roberta [1] ; Romanello, Larissa [1] ; Heleno Batista, Fernanda Aparecida [2, 3] ; Balasco Serrao, Vitor Hugo [1] ; Faheem, Muhammad [4, 5] ; Zeraik, Ana Eliza [1] ; Bird, Louise [6] ; Nettleship, Joanne [6] ; Reddivari, Yamini [6] ; Owens, Ray [6] ; DeMarco, Ricardo [1] ; Borges, Julio Cesar [2] ; Brandao-Neto, Jose [7] ; Pereira, Humberto D'Muniz [1]
Total Authors: 14
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Lab Biol Estrutural, Sao Carlos, SP - Brazil
[2] Univ Sao Paulo, Inst Quim Sao Carlos, Sao Carlos, SP - Brazil
[3] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, Campinas, SP - Brazil
[4] Univ Catolica Brasilia, Programa Pos Grad Ciencias Genom & Biotecnol, Brasilia, DF - Brazil
[5] Univ Brasilia, Dept Biol Celular, Lab Biofis Mol, Brasilia, DF - Brazil
[6] Rutherford Appleton Lab, OPPF UK, Res Complex Harwell, Oxford - England
[7] Harwell Sci & Innovat Campus, Diamond Light Source, Didcot, Oxon - England
Total Affiliations: 7
Document type: Journal article
Source: PLoS One; v. 13, n. 9 SEP 7 2018.
Web of Science Citations: 2

Purine nucleoside phosphorylases (PNPs) play an important role in the blood fluke parasite Schistosoma mansoni as a key enzyme of the purine salvage pathway. Here we present the structural and kinetic characterization of a new PNP isoform from S. mansoni, SmPNP2. Thermofluorescence screening of different ligands suggested cytidine and cytosine are potential ligands. The binding of cytosine and cytidine were confirmed by isothermal titration calorimetry, with a K-D of 27 mu M for cytosine, and a K-M of 76.3 mu M for cytidine. SmPNP2 also displays catalytic activity against inosine and adenosine, making it the first described PNP with robust catalytic activity towards both pyrimidines and purines. Crystal structures of SmPNP2 with different ligands were obtained and comparison of these structures with the previously described S. mansoni PNP (SmPNP1) provided clues for the unique capacity of SmPNP2 to bind pyrimidines. When compared with the structure of SmPNP1, substitutions in the vicinity of SmPNP2 active site alter the architecture of the nucleoside base binding site thus permitting an alternative binding mode for nucleosides, with a 180 degrees rotation from the canonical binding mode. The remarkable plasticity of this binding site enhances our understanding of the correlation between structure and nucleotide selectivity, thus suggesting new ways to analyse PNP activity. (AU)

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 type: Regular Research Grants
FAPESP's process: 12/10213-9 - Structural and functional studies of purine nucleoside phosphorylase isoform 2, Methylthioadenosine phosphorylase and participants enzymes of GTP production from purine salvage pathway from Schistosoma mansoni
Grantee:Juliana Roberta Torini de Souza
Support type: Scholarships in Brazil - Doctorate
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 type: Scholarships in Brazil - Doctorate