Please use this identifier to cite or link to this item:
- Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir
- Universidade Estadual Paulista (UNESP)
- Instituto Butantan
- Universidade Federal do Rio Grande do Sul (UFRGS)
- Pontificia Univ Catolica Rio Grande do Sul
- In human, purine nucleoside phosphorylase (HsPNP) is responsible 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 has been submitted to extensive structure-based drug design. This work reports the first crystallographic Study of human PNP complexed with acyclovir (HsPNP:Acy). Acyclovir is a potent clinically useful inhibitor of replicant herpes simplex virus that also inhibits human PNP but with a relatively lower inhibitory activity (K-i=90muM). Analysis of the structural differences among the HsPNP:Acy 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 Published by Elsevier B.V.
- Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 308, n. 3, p. 553-559, 2003.
- Elsevier B.V.
- synchrotron radiation
- drug design
- Acesso restrito
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.