Characterisation of the human serine protease HTrA1

人丝氨酸蛋白酶 HTrA1 的表征

• 批准号: 21297065
• 负责人: Professor Dr. Michael Ehrmann
• 金额: --
• 依托单位: Zentrum für Medizinische Biotechnologie (ZMB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/21297065?language=en
• 关键词: Characterisation; human; serine; protease; HTrA1

The HtrA family represents a new class of oligomeric serine proteases in which a catalytic domain is combined with one or more C-terminal PDZ domains. These proteins are widely conserved and can be found in most organisms. However, the biological implications of only some bacterial HtrAs are known while the human HtrAs are not well characterised and their precise functions are not understood. Our previous work indicated that human HtrA1 is involved in amyloid precursor protein processing, arthritis and cancer linking its function to severe human diseases. It is therefore timely to initiate studies aiming at a precise understanding of biochemical and structural properties, biological functions and its regulation. For this purpose a combination of in vitro biochemistry, crystallography, cell culture and in vivo models will be used. The latter will be instrumental to determine the basic phenotype of gene disruption and, in the future, the potency of specific HtrA1 inhibitors that could be of therapeutic relevance.

HtrA家族代表了一类新的寡聚丝氨酸蛋白酶，其催化结构域与一个或多个C-末端PDZ结构域相结合。这些蛋白质是广泛保守的，在大多数生物体中都可以找到。然而，只有一些细菌HtrA的生物学意义是已知的，而人类HtrA的特征还不是很好，它们的确切功能也不清楚。我们之前的工作表明，人类HtrA1参与淀粉样前体蛋白的加工，关节炎和癌症，将其功能与严重的人类疾病联系起来。因此，现在正是开始研究以准确了解生物化学和结构特性、生物功能及其调控的时候。为此，将使用体外生物化学、结晶学、细胞培养和体内模型的组合。后者将有助于确定基因破坏的基本表型，以及未来可能具有治疗相关性的特定HtrA1抑制剂的效力。