谷氨酸 417 残基的负电荷对 RPE65 的异构水解酶活性至关重要。
Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65.
机构信息
Department of Medicine Endocrinology, Harold Hamm Oklahoma Diabetes Center, The University of Oklahoma Health Sciences Center, 941 Stanton L Young Blvd, BSEB302, Oklahoma City, OK 73104, United States.
出版信息
Biochem Biophys Res Commun. 2010 Jan 22;391(4):1757-61. doi: 10.1016/j.bbrc.2009.12.149. Epub 2009 Dec 30.
Abstract
RPE65 is the isomerohydrolase essential for regeneration of 11-cis retinal, the chromophore of visual pigments. Here we compared the impacts of two mutations in RPE65, E417Q identified in patients with Leber congenital amaurosis (LCA), and E417D on isomerohydrolase activity. Although both mutations decreased the stability of RPE65 and altered its sub-cellular localization, E417Q abolished isomerohydrolase activity whereas the E417D mutant retained partial enzymatic activity suggesting that the negative charge of E417 is important for RPE65 catalytic activity. Loss of charge at this position may represent a mechanism by which the E417Q mutation causes blindness in LCA patients.
摘要
RPE65 是异构酶，对于 11-顺式视黄醛（视觉色素的生色团）的再生至关重要。在这里，我们比较了两种 RPE65 突变（在莱伯先天性黑蒙患者中发现的 E417Q 和 E417D）对异构酶活性的影响。尽管这两种突变均降低了 RPE65 的稳定性并改变了其亚细胞定位，但 E417Q 突变完全消除了异构酶活性，而 E417D 突变体保留了部分酶活性，这表明 E417 的负电荷对于 RPE65 的催化活性很重要。该位置上的电荷损失可能是 E417Q 突变导致 LCA 患者失明的机制之一。
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