1PWY

CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH ACYCLOVIR

Summary for 1PWY

• Entry DOI: 10.2210/pdb1pwy/pdb
• Related: 1M73 1PF7
• Descriptor: Purine nucleoside phosphorylase, SULFATE ION, 9-HYROXYETHOXYMETHYLGUANINE, ... (4 entities in total)
• Functional Keywords: purine nucleoside phosphorylase, drug design, synchrotron, acyclovir, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton : P00491
• Total number of polymer chains: 1
• Total formula weight: 32567.08

Authors

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. (deposition date: 2003-07-02, release date: 2004-03-23, Last modification date: 2023-08-16)

Primary citation

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.
Crystal structure of human purine nucleoside phosphorylase complexed with acyclovir.
Biochem.Biophys.Res.Commun., 308:553-559, 2003

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.

PubMed: 12914786
DOI: 10.1016/S0006-291X(03)01433-5

Experimental method

X-RAY DIFFRACTION (2.8 Å)