Piazza Michael, Guillemette J Guy, Dieckmann Thorsten
Department of Chemistry, University of Waterloo, 200 University Ave. W, Waterloo, ON, N2L 3G1, Canada.
Biomol NMR Assign. 2015 Oct;9(2):299-302. doi: 10.1007/s12104-015-9596-0. Epub 2015 Jan 21.
The regulation of nitric oxide synthase (NOS) by calmodulin (CaM) plays a major role in a number of key physiological and pathological processes. A detailed molecular level picture of how this regulation is achieved is critical for drug development and for our understanding of protein regulation in general. CaM is a small acidic calcium binding protein and is required to fully activate NOS. The exact mechanism of how CaM activates NOS is not fully understood at this time. Studies have shown CaM to act like a switch that causes a conformational change in NOS to allow for the electron transfer between the reductase and oxygenase domains through a process that is thought to be highly dynamic. The interaction of CaM with NOS is modified by a number of post-translation modifications including phosphorylation. Here we present backbone and sidechain (1)H, (15)N NMR assignments of modified CaM interacting with NOS peptides which provides the basis for a detailed study of CaM-NOS interaction dynamics using (15)N relaxation methods.
钙调蛋白（CaM）对一氧化氮合酶（NOS）的调节在许多关键的生理和病理过程中起着重要作用。了解这种调节是如何在分子水平上实现的详细情况，对于药物开发以及我们对一般蛋白质调节的理解至关重要。CaM是一种小的酸性钙结合蛋白，是完全激活NOS所必需的。目前尚不完全清楚CaM激活NOS的确切机制。研究表明，CaM的作用就像一个开关，通过一个被认为是高度动态的过程，引起NOS的构象变化，从而允许还原酶和加氧酶结构域之间进行电子转移。CaM与NOS的相互作用会受到包括磷酸化在内的多种翻译后修饰的影响。在此，我们展示了与NOS肽相互作用的修饰CaM的主链和侧链（1）H、（15）N NMR归属，这为使用（15）N弛豫方法详细研究CaM-NOS相互作用动力学提供了基础。
