Download MendeleyCrystal structure of human purine nucleoside phosphorylase complexed with acyclovir.
dos Santos, D.M., Canduri, F., Pereira, J.H., Vinicius Bertacine Dias, M., Silva, R.G., Mendes, M.A., Palma, M.S., Basso, L.A., de Azevedo, W.F., Santos, D.S.(2003) Biochem Biophys Res Commun 308: 553-559
- PubMed: 12914786
- DOI: https://doi.org/10.1016/s0006-291x(03)01433-5
- Primary Citation of Related Structures:
1PWY - PubMed Abstract:
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.
Organizational Affiliation:
Departamento de Física, UNESP, São José do Rio Preto, SP, Brazil.
