Nitric oxide synthase mechanism and calmodulin dependent activation

一氧化氮合酶机制和钙调蛋白依赖性激活

• 批准号: 183521-2012
• 负责人: Guillemette, Guy
• 金额: $ 2.48万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=593617
• 关键词: Nitric; oxide; synthase; mechanism; calmodulin

Nitric oxide (NO) is an important endogenous messenger in a variety of physiological and pathophysiological processes. NO is synthesized by the three isoforms of an enzyme, nitric oxide synthase (NOS) that are in part controlled by the binding of calmodulin (CaM). CaM is the primary protein mediator of the calcium cation which is also an important endogenous secondary messenger. CaM undergoes calcium concentration dependent conformational changes that allow it to differentially bind and activate scores of target proteins including the three NOS isozymes and voltage-gated calcium channels (VGCCs). Exactly how CaM manages to bind and sometimes control the activity of such a large variety of proteins and enzymes is not fully understood. The long-term objectives of this research program are to further our understanding of: 1) the mechanism and control of NO synthesis by NOS; 2) the CaM-dependent activation of its numerous target proteins including NOS isozymes and VGCCs.

一氧化氮(NO)是一种重要的内源性信使，参与多种生理和病理生理过程。NO是由一氧化氮合酶(NOS)的三种异构体合成的，这三种酶部分受钙调蛋白(CaM)的结合控制。钙调素是钙离子的主要蛋白质介体，也是重要的内源次生信使。CaM经历钙浓度依赖的构象变化，使其能够差异地结合和激活大量的靶蛋白，包括三种一氧化氮合酶同工酶和电压门控钙通道(VGCC)。CaM是如何结合并有时控制如此多种类的蛋白质和酶的活性的，目前还不完全清楚。本研究的长期目标是加深我们对以下方面的理解：1)一氧化氮合酶合成NO的机制和调控；2)其众多靶蛋白的钙调素依赖的激活，包括一氧化氮合酶同工酶和VGCC。