1PWY

CRYSTAL STRUCTURE OF HUMAN PNP COMPLEXED WITH ACYCLOVIR

1PWY の概要

• エントリーDOI: 10.2210/pdb1pwy/pdb
• 関連するPDBエントリー: 1M73 1PF7
• 分子名称: Purine nucleoside phosphorylase, SULFATE ION, 9-HYROXYETHOXYMETHYLGUANINE, ... (4 entities in total)
• 機能のキーワード: purine nucleoside phosphorylase, drug design, synchrotron, acyclovir, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton : P00491
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32567.08

構造登録者

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. (登録日: 2003-07-02, 公開日: 2004-03-23, 最終更新日: 2023-08-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)