Structural bioinformatics study of PNP from Schistosoma mansoni.
The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs.
da Silveira
Nelson José Freitas
NJ
Department of Physics, UNESP, São José do Rio Preto, SP 15054-000, Brazil.
Uchôa
Hugo Brandão
HB
Canduri
Fernanda
F
Pereira
José Henrique
JH
Camera
João Carlos
JC
Basso
Luiz Augusto
LA
Palma
Mário Sergio
MS
Santos
Diógenes Santiago
DS
de Azevedo
Walter Filgueira
WF
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D004789:Enzyme Activation; D006801:Humans; D007288:Inosine / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry*; D012550:Schistosoma mansoni / Q000201:enzymology*; D020539:Sequence Analysis, Protein / Q000379:methods*
D007288:Inosine; D011683:Purine-Nucleoside Phosphorylase