Racemization at the Asp 58 residue in αA-crystallin from the lens of high myopic cataract patients.
Racemization at the Asp 58 residue in αA-crystallin from the lens of high myopic cataract patients.
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高肌关腹患者晶状体的αA-晶状体蛋白中ASP 58残基的种族化。
DOI：
10.1111/jcmm.13363
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Zhu XJ;Zhang KK;He WW;Du Y;Hooi M;Lu Y
晶状体蛋白的翻译后修饰是白内障的关键原因。外消旋作为晶状体中含量最丰富的翻译后修饰，可能与白内障的发病机制密切相关。αA-晶体蛋白是人类晶状体中一种重要的结构和热休克蛋白，其消旋作用会显著影响其结构和功能。在先前的研究中，已经发现年龄相关性白内障晶状体中αA-晶体蛋白中从L-天冬氨酸58到d-isAsp58的消旋作用比正常老年人晶状体要高。然而，消旋化在以早发性核性白内障为特征的高度近视白内障(HMC)中的作用尚不清楚。在本研究中，与ARC明显不同的是，在α晶状体中，从L-天冬氨酸58到d-天冬氨酸58的消旋作用显著增加。计算ARC组和HMC组各Asp异构体的平均消旋率。在ARC患者中，L-天冬氨酸58向d-异天冬氨酸58的转化占消旋的主要比例，达31.89%，这与前人的研究一致。而在晶状体中，L-天冬氨酸58向d-天冬氨酸58的转化率高达35.44%，占αA-晶体蛋白外消旋的比例最大。αA-晶状体蛋白外消旋转化的不同趋势，特别是d-Asp58水平的升高，可能提示早期白内障的发生，并可能解释HMC中不同表型的白内障。
Post‐translational modifications in lens proteins are key causal factors in cataract. As the most abundant post‐translational modification in the lens, racemization may be closely related to the pathogenesis of cataract. Racemization of αA‐crystallin, a crucial structural and heat shock protein in the human lens, could significantly influence its structure and function. In previous studies, elevated racemization from l‐Asp 58 to d‐isoAsp58 in αA‐crystallin has been found in age‐related cataract (ARC) lenses compared to normal aged human lenses. However, the role of racemization in high myopic cataract (HMC), which is characterized by an early onset of nuclear cataract, remains unknown. In the current study, apparently different from ARC, significantly increased racemization from l‐Asp 58 to d‐Asp 58 in αA‐crystallin was identified in HMC lenses. The average racemization rates for each Asp isoform were calculated in ARC and HMC group. In ARC patients, the conversion of l‐Asp 58 to d‐isoAsp 58, up to 31.89%, accounted for the main proportion in racemization, which was in accordance with the previous studies. However, in HMC lenses, the conversion of l‐Asp 58 to d‐Asp 58, as high as 35.44%, accounted for the largest proportion of racemization in αA‐crystallin. The different trend in the conversion of αA‐crystallin by racemization, especially the elevated level of d‐Asp 58 in HMC lenses, might prompt early cataractogenesis and a possible explanation of distinct phenotypes of cataract in HMC.
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影响因子：
4.4
作者：
Hooi, Michelle Yu Sung;Raftery, Mark J.;Truscott, Roger John Willis
通讯作者：
Truscott, Roger John Willis
影响因子：
4.4
作者：
Hains, Peter G.;Truscott, Roger J. W.
通讯作者：
Truscott, Roger J. W.
影响因子：
--
作者：
Shui, Ying-Bo;Holekamp, Nancy M.;Kramer, Benjamin C.;Crowley, Jan R.;Wilkins, Mark A.;Chu, Fred;Malone, Paula E.;Mangers, Shayna J.;Hou, Joshua H.;Siegfried, Carla J.;Beebe, David C.
通讯作者：
Beebe, David C.
影响因子：
8
作者：
Takata, Takumi;Oxford, Julie T.;Lampi, Kirsten J.
通讯作者：
Lampi, Kirsten J.
DOI：
10.1016/j.bbagen.2009.05.008
发表时间：
2009-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Sharma KK;Santhoshkumar P
通讯作者：
Santhoshkumar P