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- Structural basis for inhibition of human PNP by immucillin-H
- Universidade Estadual Paulista (UNESP)
- Instituto Butantan
- Universidade Federal do Rio Grande do Sul (UFRGS)
- Pontificia Univ Catolica Rio Grande Sul
- 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.
- Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 309, n. 4, p. 917-922, 2003.
- Elsevier B.V.
- synchrotron radiation
- drug design
- Acesso restrito
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