Crystal structure of human PNP complexed with guanine
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Data
2003-12-19
Autores
de Azevedo, W. F.
Canduri, F.
dos Santos, D. M.
Pereira, J. H.
Dias, MVB
Silva, R. G.
Mendes, M. A.
Basso, L. 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. PNP is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. More recently, the 3-D structure of human PNP has been refined to 2.3 Angstrom resolution, which allowed a redefinition of the residues involved in the substrate-binding sites and provided a more reliable model for structure-based design of inhibitors. This work reports crystallographic study of the complex of Human PNP:guanine (HsPNP:Gua) solved at 2.7 Angstrom resolution using synchrotron radiation. Analysis of the structural differences among the HsPNP:Gua complex, PNP apoenzyme, and HsPNP:immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design. (C) 2003 Elsevier B.V. All rights reserved.
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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. 312, n. 3, p. 767-772, 2003.