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首页> 外文期刊>Biochemistry >Structural Studies of a Complex Between Endothelial Nitric Oxide Synthase and Calmodulin at Physiological Calcium Concentration
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Structural Studies of a Complex Between Endothelial Nitric Oxide Synthase and Calmodulin at Physiological Calcium Concentration

机译：生理钙浓度下内皮型一氧化氮合酶与钙调蛋白复合物的结构研究

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The small acidic protein calmodulin (CaM) serves as a Ca2+ sensor and control element for many enzymes including nitric oxide synthase (NOS) enzymes that play major roles in key physiological and pathological processes. CaM binding 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. In this report, NMR spectroscopy was used to determine the solution structure of the endothelial NOS (eNOS) peptide in complex with CaM at the lowest Ca2+ concentration (225 nM) required for CaM to bind to eNOS and corresponds to a physiological elevated Ca2+ level found in mammalian cells. Under these conditions, the CaM eNOS complex has a Ca2+-replete C-terminal lobe bound to the eNOS peptide and a Ca2+ free N-terminal lobe loosely associated with the eNOS peptide. With increasing Ca2+ concentration, the binding of Ca2+ by the N-lobe of CaM results in a stronger interaction with the C-terminal region of the eNOS peptide and increased alpha-helical structure of the peptide that may be part of the mechanism resulting in electron transfer from the FMN to the heme in the oxygenase domain of the enzyme. Surface plasmon resonance studies performed under the same conditions show Ca2+ concentration-dependent binding kinetics were consistent with the NMR structural results. This investigation shows that structural studies performed under more physiological relevant conditions provide information on subtle changes in structure that may not be apparent when experiments are performed in excess Ca2+ concentrations.
机译：小型酸性蛋白质钙调蛋白（CaM）充当Ca2 +传感器和许多酶的控制元件，包括一氧化氮合酶（NOS）酶，这些酶在关键的生理和病理过程中起主要作用。 CaM结合导致NOS发生构象变化，以允许电子在还原酶和氧化酶结构域之间转移。通过被认为是高度动态的过程。在此报告中，使用NMR光谱确定了CaM结合eNOS所需的最低Ca2 +浓度（225 nM）下与CaM形成复合的内皮NOS（eNOS）肽的溶液结构，这对应于发现的生理升高的Ca2 +水平在哺乳动物细胞中。在这些条件下，CaM eNOS复合物具有与eNOS肽结合的Ca2 +完整的C末端叶和与eNOS肽松散相关的无Ca2 +的N末端叶。随着Ca2 +浓度的增加，CaM的N瓣与Ca2 +的结合会导致与eNOS肽C端区域的相互作用更强，并且该肽的α-螺旋结构增加，这可能是产生电子的机制的一部分在酶的加氧酶结构域中从FMN转移到血红素。在相同条件下进行的表面等离振子共振研究表明，Ca2 +浓度依赖性的结合动力学与NMR结构结果一致。这项研究表明，在更多生理相关条件下进行的结构研究提供了有关结构细微变化的信息，而这些实验在过量的Ca2 +浓度下进行时可能并不明显。

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