Calpain chronicle--an enzyme family under multidisciplinary characterization.

Calpain chronicle--an enzyme family under multidisciplinary characterization.
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DOI:
10.2183/pjab.87.287
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发表时间:
2011
期刊:
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子:
--
通讯作者:
Ono Y
Ono Y
中科院分区:
其他
文献类型:
--
作者:
Sorimachi H;Hata S;Ono Y

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Calpain是一种细胞内Ca2+依赖性半胱氨酸蛋白酶(EC 3.4.22.17; Clan CA, family co2),发现于1964年。1990年以前又称CANP (Ca2+-activated neutral protease),也称CASF、CDP、KAF等。钙蛋白存在于几乎所有真核生物和少数细菌中,但不存在于古细菌中。calpain具有有限的蛋白水解活性,其功能是改变或调节其底物的结构和活性;因此,它们被称为“调节蛋白酶”。在人类基因组中,有15个基因- capn1, CAPN2等-编码calpain样蛋白酶结构域。它们的产物是钙蛋白酶同源物,具有不同的结构和各种功能域的组合,包括Ca2+结合和微管相互作用域。遗传学研究已经将钙蛋白酶缺乏与许多不同生物体的各种缺陷联系起来,包括致命性、肌肉萎缩症、胃病和糖尿病。本文综述了calpain的研究,重点介绍了其结构-功能关系的最新发现。这些发现在很大程度上得益于三维结构研究和遗传模型的发展。
Calpain is an intracellular Ca2+-dependent cysteine protease (EC 3.4.22.17; Clan CA, family C02) discovered in 1964. It was also called CANP (Ca2+-activated neutral protease) as well as CASF, CDP, KAF, etc. until 1990. Calpains are found in almost all eukaryotes and a few bacteria, but not in archaebacteria. Calpains have a limited proteolytic activity, and function to transform or modulate their substrates’ structures and activities; they are therefore called, “modulator proteases.” In the human genome, 15 genes—CAPN1, CAPN2, etc.—encode a calpain-like protease domain. Their products are calpain homologs with divergent structures and various combinations of functional domains, including Ca2+-binding and microtubule-interaction domains. Genetic studies have linked calpain deficiencies to a variety of defects in many different organisms, including lethality, muscular dystrophies, gastropathy, and diabetes. This review of the study of calpains focuses especially on recent findings about their structure–function relationships. These discoveries have been greatly aided by the development of 3D structural studies and genetic models.
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