3INY

Crystal structure of human purine nucleoside phosphorylase in complex with 7-deazaguanine

3INY の概要

• エントリーDOI: 10.2210/pdb3iny/pdb
• 関連するPDBエントリー: 1V41
• 分子名称: Purine nucleoside phosphorylase, SULFATE ION, 7-DEAZAGUANINE, ... (4 entities in total)
• 機能のキーワード: 7-deazaguanine, cytoskeleton, disease mutation, glycosyltransferase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton (By similarity): P00491
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32623.20

構造登録者

de Azevedo Jr, W.F.,Santos, D.S.,Basso, L.A. (登録日: 2009-08-13, 公開日: 2011-01-19, 最終更新日: 2023-09-06)

主引用文献

Caceres, R.A.,Timmers, L.F.,Pauli, I.,Gava, L.M.,Ducati, R.G.,Basso, L.A.,Santos, D.S.,de Azevedo, W.F.
Crystal structure and molecular dynamics studies of human purine nucleoside phosphorylase complexed with 7-deazaguanine.
J.Struct.Biol., 169:379-388, 2010

PubMed Abstract: In humans, purine nucleoside phosphorylase (HsPNP) is responsible for degradation of deoxyguanosine, and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. HsPNP is a target for inhibitor development aiming at T-cell immune response modulation. Here we report the crystal structure of HsPNP in complex with 7-deazaguanine (HsPNP:7DG) at 2.75 A. Molecular dynamics simulations were employed to assess the structural features of HsPNP in both free form and in complex with 7DG. Our results show that some regions, responsible for entrance and exit of substrate, present a conformational variability, which is dissected by dynamics simulation analysis. Enzymatic assays were also carried out and revealed that 7-deazaguanine presents a lower inhibitory activity against HsPNP (K(i)=200 microM). The present structure may be employed in both structure-based design of PNP inhibitors and in development of specific empirical scoring functions.

PubMed: 19932753
DOI: 10.1016/j.jsb.2009.11.010

実験手法

X-RAY DIFFRACTION (2.75 Å)