1pwy: Difference between revisions

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)=90 microM). 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.

[[Category: Azevedo, W F.De.]]

[[Category: Basso, L A.]]

[[Category: Dias, M Vinicius Bertacine.]]

[[Category: Mendes, M A.]]

[[Category: Palma, M S.]]

[[Category: Pereira, J H.]]

[[Category: Santos, D M.Dos.]]

[[Category: Santos, D S.]]

[[Category: Silva, R G.]]

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