哺乳类动物中血红素蛋白调控的硫化物新陈代谢机理

项目名称： 哺乳类动物中血红素蛋白调控的硫化物新陈代谢机理

项目编号： No.21271104

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 易军

作者单位： 南京理工大学

项目金额： 78万元

中文摘要： 虽然研究表明不同的硫化物可以与哺乳动物体内的血红素蛋白发生反应，然而至今还没有任何有关人体内血红素蛋白通过铁活性中心介导的含硫化合物新陈代谢（硫循环）过程机理的研究报道，这一知识空白极大阻碍了人们对若干与硫的生理或病理相关疾病起因的深入理解。本项目的目标是确定肌球蛋白（肌肉中）和血红蛋白（血液内）铁活性中心对硫化物之间转化反应的控制因素，并研究过量硫化物对该类血红素蛋白结构与功能的影响。本项目拟表达、分离和纯化在肌球蛋白控制的硫代谢过程中可能产生的一系列中间产物；拟采用野生型、再造型及突变型肌球蛋白，通过改变活性中心氢键数目与位置以及改变血红素大环结构，精确分析蛋白活性中心对硫化物结构的影响；并研究体内过量硫化物对血红素蛋白结构影响所导致的硫血红素蛋白血症形成的机理。研究结果将为含硫配体的血红素蛋白的结构与功能的关联、以及血红素蛋白调控的硫化物新陈代谢的机理提供重要的新信息和结构依据。

中文关键词： 硫化物；血红素；结构功能；肌红蛋白；血红蛋白

英文摘要： Sulfur is a critical element for human health, and is present in the amino acids cysteine, methionine, homocysteine, and in a variety of iron-sulfur electron transfer proteins. Interestingly, it is now known that the terminal product of sulfite reduction, namely hydrogen sulfide (H2S), is also biosynthesized in humans! This pungent smelly gas has been proposed to be a physiological signaling molecule for vasodilation in humans, in addition to being implicated in neurotransmission, inflammation, and in diabetes. There is growing evidence of reactions of various sulfur-containing compounds with human and mammalian heme proteins. However, to the best of our knowledge, there have been no studies on the iron-mediated sulfur metabolism by human and mammalian heme proteins. This represents a significant gap in knowledge, and the lack of understanding negatively impacts our ability to accurately determine the causes of various ailments associated with the physiology and pathology of sulfur. Our long-term goal is to delineate the role that the iron (Fe) center in heme proteins play in the metabolism of biologically important small molecules, and our recent work has focused on the heme-mediated biological chemistry of various NOx species associated with vasodilation, nitriheme formation, and nitrite-induced heme los

英文关键词： sulfur compound；heme；structure-function；myoglobin；hemoglobin