Crystal structure of human purine nucleoside phosphorylase at 2.3 angstrom resolution
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Data
2003-08-29
Autores
de Azevedo, W. F.
Canduri, F.
dos Santos, D. M.
Silva, R. G.
de Oliveira, J. S.
de Carvalho, LPS
Basso, L. A.
Mendes, M. A.
Palma, Mario Sergio [UNESP]
Santos, D. S.
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Editor
Elsevier B.V.
Resumo
Purine 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.
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PNP, synchrotron radiation, Structure, drug design
Como citar
Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 308, n. 3, p. 545-552, 2003.