de Azevedo, W. F.Canduri, F.dos Santos, D. M.Pereira, J. H.Dias, MVBSilva, R. G.Mendes, M. A.Basso, L. A.Palma, Mario Sergio [UNESP]Santosce, D. S.2014-05-202014-05-202003-10-03Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 309, n. 4, p. 917-922, 2003.0006-291Xhttp://hdl.handle.net/11449/19907Purine 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.917-922engPNPsynchrotron radiationStructureimmucillin-Hdrug designArtigo10.1016/j.bbrc.2003.08.094WOS:000185774300032Acesso restrito94241756882065452901888624506535