Publicação: Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir
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Elsevier B.V.
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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.
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PNP, synchrotron radiation, Structure, acyclovir, drug design
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Inglês
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Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 308, n. 3, p. 553-559, 2003.
