한빛사논문
- 조회1,064
SeHee Park1, Erin E. Doherty1, Yixuan Xie1, Anil K. Padyana2, Fang Fang3, Yue Zhang1, Agya Karki1, Carlito B. Lebrilla1,4, Justin B. Siegel1,4,5 & Peter A. Beal1,*
1Department of Chemistry, University of California, Davis, Davis, CA, USA.
2Agios Pharmaceuticals, Cambridge, MA, USA.
3Viva Biotech Ltd., Shanghai, China.
4Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, USA. 5Genome Center, University of California Davis, Davis, CA, USA.
*Corresponding author
Abstract
Adenosine Deaminases that act on RNA (ADARs) are enzymes that catalyze adenosine to inosine conversion in dsRNA, a common form of RNA editing. Mutations in the human ADAR1 gene are known to cause disease and recent studies have identified ADAR1 as a potential therapeutic target for a subset of cancers. However, efforts to define the mechanistic effects for disease associated ADAR1 mutations and the rational design of ADAR1 inhibitors are limited by a lack of structural information. Here, we describe the combination of high throughput mutagenesis screening studies, biochemical characterization and Rosetta-based structure modeling to identify unique features of ADAR1. Importantly, these studies reveal a previously unknown zinc-binding site on the surface of the ADAR1 deaminase domain which is important for ADAR1 editing activity. Furthermore, we present structural models that explain known properties of this enzyme and make predictions about the role of specific residues in a surface loop unique to ADAR1.
논문정보
- Research article
- 2020년 10월 (BRIC 등록일 2020-10-20)
- 국외 연구진
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