Abstract
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 α-helix and variable-length loops separated by several small β-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.
Keywords: Ubiquitin, E3 ubiquitin ligase, RING finger, zinc-coordination, anticancer drugs
Current Pharmaceutical Design
Title: RING Finger E3 Ubiquitin Ligases: Structure and Drug Discovery
Volume: 15 Issue: 31
Author(s): Christos T. Chasapis and Georgios A. Spyroulias
Affiliation:
Keywords: Ubiquitin, E3 ubiquitin ligase, RING finger, zinc-coordination, anticancer drugs
Abstract: 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 α-helix and variable-length loops separated by several small β-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.
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Cite this article as:
Chasapis T. Christos and Spyroulias A. Georgios, RING Finger E3 Ubiquitin Ligases: Structure and Drug Discovery, Current Pharmaceutical Design 2009; 15 (31) . https://dx.doi.org/10.2174/138161209789271825
DOI https://dx.doi.org/10.2174/138161209789271825 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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