Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM d...Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.展开更多
目的:了解2018—2020年菏泽市猪、牛、羊肉中β-受体激动剂残留状况并开展暴露风险评估,为加强监管提供科学依据。方法:2018—2020年,连续3年采集农贸市场、超市及冷鲜肉专卖店的猪牛羊肉样品共532份,进行克伦特罗、莱克多巴胺、沙丁胺...目的:了解2018—2020年菏泽市猪、牛、羊肉中β-受体激动剂残留状况并开展暴露风险评估,为加强监管提供科学依据。方法:2018—2020年,连续3年采集农贸市场、超市及冷鲜肉专卖店的猪牛羊肉样品共532份,进行克伦特罗、莱克多巴胺、沙丁胺醇和特布他林4种β-受体激动剂的检测,并使用安全限值法(Margin of Safety,MOS)开展暴露风险评估。结果:3年间猪、牛、羊肉中4种β-受体激动剂的总检出率为6.58%,检出项目均为克伦特罗;牛肉中克伦特罗的检出率逐年下降,检出率差异有统计学意义(P<0.05);羊肉中的检出率逐年上升,检出率差异有统计学意义(P<0.05)。猪肉中的检出率略有上升,检出率差异无统计学意义(P>0.05)。统计结果表明,克伦特罗在猪、牛、羊肉3种肉中的检出率差异无统计学意义(P>0.05)。2018年除牛肉外,猪肉、羊肉中克伦特罗的MOS值均大于1;2019年、2020年猪、牛、羊肉的MOS值均小于1。结论:菏泽市畜肉中β-受体激动剂检出项目为克伦特罗,2018—2020年羊肉中克伦特罗的检出率呈连年上升的趋势,2018年克伦特罗对猪肉、羊肉安全的影响在不可以接受的程度内,需进一步提高对畜肉市场的监管力度,严禁瘦肉精类药品的非法滥用,保障食品安全。展开更多
基金National Natural Science Foundation of China(22073030)the Oriental Scholars of Shanghai Universities。
文摘Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.
文摘目的:了解2018—2020年菏泽市猪、牛、羊肉中β-受体激动剂残留状况并开展暴露风险评估,为加强监管提供科学依据。方法:2018—2020年,连续3年采集农贸市场、超市及冷鲜肉专卖店的猪牛羊肉样品共532份,进行克伦特罗、莱克多巴胺、沙丁胺醇和特布他林4种β-受体激动剂的检测,并使用安全限值法(Margin of Safety,MOS)开展暴露风险评估。结果:3年间猪、牛、羊肉中4种β-受体激动剂的总检出率为6.58%,检出项目均为克伦特罗;牛肉中克伦特罗的检出率逐年下降,检出率差异有统计学意义(P<0.05);羊肉中的检出率逐年上升,检出率差异有统计学意义(P<0.05)。猪肉中的检出率略有上升,检出率差异无统计学意义(P>0.05)。统计结果表明,克伦特罗在猪、牛、羊肉3种肉中的检出率差异无统计学意义(P>0.05)。2018年除牛肉外,猪肉、羊肉中克伦特罗的MOS值均大于1;2019年、2020年猪、牛、羊肉的MOS值均小于1。结论:菏泽市畜肉中β-受体激动剂检出项目为克伦特罗,2018—2020年羊肉中克伦特罗的检出率呈连年上升的趋势,2018年克伦特罗对猪肉、羊肉安全的影响在不可以接受的程度内,需进一步提高对畜肉市场的监管力度,严禁瘦肉精类药品的非法滥用,保障食品安全。
