Members of the multiple antibiotic resistance regulator(MarR)protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance.MarR family proteins function ...Members of the multiple antibiotic resistance regulator(MarR)protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance.MarR family proteins function as repressors,and their interactions with modulators induce the expression of controlled genes.The previously characterized modulators are insufficient to explain the activities of certain MarR family proteins.However,recently,several MarR family proteins have been reported to sense sulfane sulfur,including zero-valent sulfur,persulfide(R-SSH),and polysulfide(R-SnH,n≥2).Sulfane sulfur is a common cellular component in bacteria whose levels vary during bacterial growth.The changing levels of sulfane sulfur affect the expression of many MarR-controlled genes.Sulfane sulfur reacts with the cysteine thiols of MarR family proteins,causing the formation of protein thiol persulfide,disulfide bonds,and other modifications.Several MarR family proteins that respond to reactive oxygen species(ROS)also sense sulfane sulfur,as both sulfane sulfur and ROS induce the formation of disulfide bonds.This review focused on MarR family proteins that sense sulfane sulfur.However,the sensing mechanisms reviewed here may also apply to other proteins that detect sulfane sulfur,which is emerging as a modulator of gene regulation.展开更多
This paper reviews milestones in antidotal therapies for cyanide(CN) spanning early remedies,current antidotal systems and research towards next generation therapies.CN has been a part of plant defense mechanisms for ...This paper reviews milestones in antidotal therapies for cyanide(CN) spanning early remedies,current antidotal systems and research towards next generation therapies.CN has been a part of plant defense mechanisms for millions of years.It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent.The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929.These fundamental studies led to a variety of antidotes,including indirect CN binders that generate methemoglobin,direct CN binders such as hydroxocobalamin,and sulfur donors that convert CN to the less toxic thiocyanate.Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide(NO) in the body.The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites.Presently used CN therapies include:methemoglobin/NO generators(e.g.,sodium nitrite,amyl nitrite,and dimethyl aminophenol),sulfur donors(e.g.,sodium thiosulfate and glutathione),and direct binding agents [(e.g.,hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid(dicobalt edetate)].A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios.New antidotes,formulations,and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures.展开更多
基金supported by the National Natural Science Foundation of China(Nos.92351302,91951202,and 32201982).
文摘Members of the multiple antibiotic resistance regulator(MarR)protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance.MarR family proteins function as repressors,and their interactions with modulators induce the expression of controlled genes.The previously characterized modulators are insufficient to explain the activities of certain MarR family proteins.However,recently,several MarR family proteins have been reported to sense sulfane sulfur,including zero-valent sulfur,persulfide(R-SSH),and polysulfide(R-SnH,n≥2).Sulfane sulfur is a common cellular component in bacteria whose levels vary during bacterial growth.The changing levels of sulfane sulfur affect the expression of many MarR-controlled genes.Sulfane sulfur reacts with the cysteine thiols of MarR family proteins,causing the formation of protein thiol persulfide,disulfide bonds,and other modifications.Several MarR family proteins that respond to reactive oxygen species(ROS)also sense sulfane sulfur,as both sulfane sulfur and ROS induce the formation of disulfide bonds.This review focused on MarR family proteins that sense sulfane sulfur.However,the sensing mechanisms reviewed here may also apply to other proteins that detect sulfane sulfur,which is emerging as a modulator of gene regulation.
基金Robert A.Welch Foundation(x-0011)at Sam Houston State University
文摘This paper reviews milestones in antidotal therapies for cyanide(CN) spanning early remedies,current antidotal systems and research towards next generation therapies.CN has been a part of plant defense mechanisms for millions of years.It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent.The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929.These fundamental studies led to a variety of antidotes,including indirect CN binders that generate methemoglobin,direct CN binders such as hydroxocobalamin,and sulfur donors that convert CN to the less toxic thiocyanate.Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide(NO) in the body.The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites.Presently used CN therapies include:methemoglobin/NO generators(e.g.,sodium nitrite,amyl nitrite,and dimethyl aminophenol),sulfur donors(e.g.,sodium thiosulfate and glutathione),and direct binding agents [(e.g.,hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid(dicobalt edetate)].A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios.New antidotes,formulations,and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures.