Suppr超能文献

硝酰介导的硫醇蛋白破坏:对酵母转录因子Ace1的抑制作用

Nitroxyl-mediated disruption of thiol proteins: inhibition of the yeast transcription factor Ace1.

作者信息

Cook Natalie M, Shinyashiki Masaru, Jackson Matthew I, Leal Felipe A, Fukuto Jon M

机构信息

Department of Pharmacology, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA 90095-1735, USA.

出版信息

Arch Biochem Biophys. 2003 Feb 1;410(1):89-95. doi: 10.1016/s0003-9861(02)00656-2.

Abstract

Among the biologically and pharmacologically relevant nitrogen oxides, nitroxyl (HNO) remains one of the most poorly studied and least understood. Several previous reports indicate that thiols may be a primary target for the biological actions of HNO. However, the intimate details of the chemical interaction of HNO with biological thiols remain unestablished. Due to their ability to grow under a variety of conditions, the yeast Saccharomyces cerevisiae represents a unique and useful model system for examining the chemistry of HNO with thiol proteins in a whole-cell preparation. Herein, we have examined the effect of HNO on the thiol-containing, metal-responsive, yeast transcription factor Ace1 under a variety of cellular conditions as a means of delineating the chemistry of HNO interactions with this representative thiol protein. Using a reporter gene system, we find that HNO efficiently inhibits copper-dependent Ace1 activity. Moreover, this inhibition appears to be a result of a direct interaction between Ace1 thiols and HNO and not a result of any chemistry associated with HNO-derived species. Thus, this report indicates that thiol proteins can be a primary target of HNO biochemistry and that HNO-mediated thiol modification is likely due to a direct reaction of HNO.

摘要

在具有生物学和药理学相关性的氮氧化物中,硝酰(HNO)仍然是研究最少、了解最浅的物质之一。先前的几份报告表明,硫醇可能是HNO生物学作用的主要靶点。然而,HNO与生物硫醇化学相互作用的具体细节仍未明确。由于酵母酿酒酵母能够在多种条件下生长,它代表了一种独特且有用的模型系统,用于在全细胞制剂中研究HNO与含硫醇蛋白质的化学反应。在此,我们研究了在多种细胞条件下HNO对含硫醇、金属反应性酵母转录因子Ace1的影响,以此来描述HNO与这种代表性硫醇蛋白相互作用的化学过程。使用报告基因系统,我们发现HNO能有效抑制铜依赖性Ace1活性。此外,这种抑制似乎是Ace1硫醇与HNO直接相互作用的结果,而非与HNO衍生物种相关的任何化学反应的结果。因此,本报告表明硫醇蛋白可能是HNO生物化学的主要靶点,并且HNO介导的硫醇修饰可能是由于HNO的直接反应。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验