【摘 要】
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11-beta hydroxysteroid dehydrogenase type Ⅰ (11β-HSD 1) is an ER-membrane associated short-chain reductase that catalyzes the conversion of cortisone to cortisol,a stress hormone associated with vario
【机 构】
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Pfizer Global R & D, San Diego USA
【出 处】
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2008中国深圳蛋白质和多肽科学大会
论文部分内容阅读
11-beta hydroxysteroid dehydrogenase type Ⅰ (11β-HSD 1) is an ER-membrane associated short-chain reductase that catalyzes the conversion of cortisone to cortisol,a stress hormone associated with various biological and pathological processes.Increasing evidence suggests that 11 β-HSD1 is an attractive therapeutic target for a number of metabolic disorders such as diabetes and obesity.Nevertheless,the hydrophobic nature of this enzyme presents a significant hurdle to produce active and sufficient recombinant protein for high throughput screen and structural determination.In this communication,we describe a rational mutagenesis approach that allowed us to express and purify human 11β-HSD1 enzyme from E.coli with high yield,solubility,activity,and homogeneity,which thus greatly facilitated the downstream process in identification and optimization of novel drug candidates.
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