Structural basis for inhibition of human PNP by immucillin-H
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Data
2003-10-03
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]
Santosce, 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. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6 Angstrom resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP. (C) 2003 Elsevier B.V. All rights reserved.
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Palavras-chave
PNP, synchrotron radiation, Structure, immucillin-H, drug design
Como citar
Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 309, n. 4, p. 917-922, 2003.