de Azevedo, W. F.Canduri, F.dos Santos, D. M.Silva, R. G.de Oliveira, J. S.de Carvalho, LPSBasso, L. A.Mendes, M. A.Palma, Mario Sergio [UNESP]Santos, D. S.2014-05-202014-05-202003-08-29Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 308, n. 3, p. 545-552, 2003.0006-291Xhttp://hdl.handle.net/11449/19546Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. In human, PNP is the only route for degradation of deoxyguanosine and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and its low resolution structure has been used for drug design. Here we report the structure of human PNP solved to 2.3 Angstrom resolution using synchrotron radiation and cryocrystallographic techniques. This structure allowed a more precise analysis of the active site, generating a more reliable model for substrate binding. The higher resolution data allowed the identification of water molecules in the active site, which suggests binding partners for potential ligands. Furthermore, the present structure may be used in the new structure-based design of PNP inhibitors. (C) 2003 Published by Elsevier B.V.545-552engPNPsynchrotron radiationStructuredrug designArtigo10.1016/S0006-291X(03)01431-1WOS:000184945400023Acesso restrito94241756882065452901888624506535