Department of Pharmacy, University of Patras, Panepistimioupoli - Rion, GR-26504, Patras, Greece.
Curr Pharm Des. 2009;15(31):3716-31. doi: 10.2174/138161209789271825.
The RING (Really Interesting New Gene) family is the largest type of E3 ubiquitin ligases. RING finger domains bind two zinc ions in a unique "cross-brace" arrangement through a defined motif of cysteine and histidine residues. This arrangement endows the RING domain with a globular conformation, characterized by a central alpha-helix and variable-length loops separated by several small beta-strands. RING E3 ubiquitin ligases, play an essential role in the regulation of many biologic processes and defects in some of them are involved in cancer development. Furthermore, some RING E3 ligases are frequently overexpressed in human cancers. Today, RING ligases represent potentially molecular targets for disease intervention and could act as prognostic biomarkers. Targeting specific RING E3 ligases could lead to the development of a novel class of anticancer drugs. However RING fingers exhibit remarkable variations in their sequence and their topology characteristics. Structure determination of new RING finger domain is in the core of the design of new pharmaceuticals and what is presented in this article is a thorough review of achievements on the NMR or Xray structure determinations. Protein preparation protocols along with analysis of the structural features of known RING finger are also presented.
RING（真正有趣的新基因）家族是最大的 E3 泛素连接酶类型。RING 指结构域通过特定的半胱氨酸和组氨酸残基模体以独特的“交叉支撑”排列结合两个锌离子。这种排列赋予 RING 结构域一个球形构象，其特征是中央α-螺旋和由几个小β-链隔开的可变长度环。RING E3 泛素连接酶在许多生物过程的调节中起着至关重要的作用，其中一些缺陷涉及癌症的发展。此外，一些 RING E3 连接酶在人类癌症中经常过度表达。如今，RING 连接酶代表潜在的疾病干预的分子靶标，并可以作为预后生物标志物。针对特定的 RING E3 连接酶可能会导致新型抗癌药物的开发。然而，RING 指在其序列和拓扑特征上表现出显著的变化。新 RING 指结构域的结构测定是设计新药物的核心，本文全面回顾了 NMR 或 X 射线结构测定方面的成果。还介绍了蛋白质制备方案以及已知 RING 指结构特征的分析。
