Structural Discovery of Small Molecule Binding Sites in Cu-Zn Human Superoxide Dismutase Familial Amyotrophic Lateral Sclerosis Mutants Provides Insights for Lead Optimization

被引：30

作者：

Antonyuk, Svetlana ^{[1
]}

Strange, Richard W. ^{[1
]}

Hasnain, S. Samar ^{[1
]}

机构：

[1] Univ Liverpool, Sch Biol Sci, Mol Biophys Grp, Liverpool L69 7ZB, Merseyside, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 03期

关键词：

SOD1; AGGREGATION;

D O I：

10.1021/jm9017948

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dominant inheritance of point mutations in CuZn superoxide dismutase (SOD1) is the best characterized subset of familial amyotrophic lateral sclerosis (FALS) and accounts for some 20% of the known familial cases. We report the discovery and visualization via cocrystallography of two ligand-binding pockets in human SOD1 and its pathogenic mutants that have opened up the real possibility of undertaking lead compound discovery using a fragment-based approach for therapeutic purposes for SOD1 associated motor neuron disease.

引用

页码：1402 / 1406

页数：5