1OUM

M64V PNP +Talo

1OUM の概要

• エントリーDOI: 10.2210/pdb1oum/pdb
• 関連するPDBエントリー: 1A9O 1ECP 1OTX 1OTY 1OU4 1OV6 1OVG
• 分子名称: Purine nucleoside phosphorylase, 9-(6-DEOXY-ALPHA-L-TALOFURANOSYL)-6-METHYLPURINE, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: m64v, pnp, talo, transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 78486.83

構造登録者

Ealick, S.E.,Bennett, E.M.,Anand, R.,Secrist, J.A.,Parker, W.B.,Hassan, A.E.,Allan, P.W.,McPherson, D.T.,Sorscher, E.J. (登録日: 2003-03-24, 公開日: 2004-02-17, 最終更新日: 2024-02-14)

主引用文献

Bennett, E.M.,Anand, R.,Allan, P.W.,Hassan, A.E.,Hong, J.S.,Levasseur, D.N.,McPherson, D.T.,Parker, W.B.,Secrist, J.A.,Sorscher, E.J.,Townes, T.M.,Waud, W.R.,Ealick, S.E.
Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system.
Chem.Biol., 10:1173-1181, 2003

PubMed Abstract: Activation of prodrugs by Escherichia coli purine nucleoside phosphorylase (PNP) provides a method for selectively killing tumor cells expressing a transfected PNP gene. This gene therapy approach requires matching a prodrug and a known enzymatic activity present only in tumor cells. The specificity of the method relies on avoiding prodrug cleavage by enzymes already present in the host cells or the intestinal flora. Using crystallographic and computer modeling methods as guides, we have redesigned E. coli PNP to cleave new prodrug substrates more efficiently than does the wild-type enzyme. In particular, the M64V PNP mutant cleaves 9-(6-deoxy-alpha-L-talofuranosyl)-6-methylpurine with a kcat/Km over 100 times greater than for native E. coli PNP. In a xenograft tumor experiment, this compound caused regression of tumors expressing the M64V PNP gene.

PubMed: 14700625
DOI: 10.1016/j.chembiol.2003.11.008

実験手法

X-RAY DIFFRACTION (2.4 Å)