1PR2

Escherichia coli Purine Nucleoside Phosphorylase Complexed with 9-beta-D-[2-deoxyribofuranosyl]-6-methylpurine and Phosphate/Sulfate

1PR2 の概要

• エントリーDOI: 10.2210/pdb1pr2/pdb
• 関連するPDBエントリー: 1ECP 1K9S 1PK7 1PR0 1PR1 1PR4 1PR5 1PR6
• 分子名称: Purine nucleoside phosphorylase DeoD-type, PHOSPHATE ION, 9-(2-DEOXY-BETA-D-RIBOFURANOSYL)-6-METHYLPURINE, ... (4 entities in total)
• 機能のキーワード: protein-nucleoside complex, transferase
• 由来する生物種: Escherichia coli O157:H7
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 78981.52

構造登録者

Bennett, E.M.,Li, C.,Allan, P.W.,Parker, W.B.,Ealick, S.E. (登録日: 2003-06-19, 公開日: 2003-11-25, 最終更新日: 2023-08-16)

主引用文献

Bennett, E.M.,Li, C.,Allan, P.W.,Parker, W.B.,Ealick, S.E.
Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase.
J.Biol.Chem., 278:47110-47118, 2003

PubMed Abstract: Purine nucleoside phosphorylase catalyzes reversible phosphorolysis of purine nucleosides and 2'-deoxypurine nucleosides to the free base and ribose (or 2'-deoxyribose) 1-phosphate. Whereas the human enzyme is specific for 6-oxopurine ribonucleosides, the Escherichia coli enzyme accepts additional substrates including 6-oxopurine ribonucleosides, 6-aminopurine ribonucleosides, and to a lesser extent purine arabinosides. These differences have been exploited in a potential suicide gene therapy treatment for solid tumors. In an effort to optimize this suicide gene therapy approach, we have determined the three-dimensional structure of the E. coli enzyme in complex with 10 nucleoside analogs and correlated the structures with kinetic measurements and computer modeling. These studies explain the preference of the enzyme for ribose sugars, show increased flexibility for active site residues Asp204 and Arg24, and suggest that interactions involving the 1- and 6-positions of the purine and the 4'- and 5'-positions of the ribose provide the best opportunities to increase prodrug specificity and enzyme efficiency.

PubMed: 12937174
DOI: 10.1074/jbc.M304622200

実験手法

X-RAY DIFFRACTION (2.3 Å)