...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mechanisms of ammonia activation and ammonium ion inhibition of quinoprotein methanol dehydrogenase: a computational approach.
【24h】

Mechanisms of ammonia activation and ammonium ion inhibition of quinoprotein methanol dehydrogenase: a computational approach.

机译：氨激活喹蛋白甲醇脱氢酶和铵离子抑制的机制：一种计算方法。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The mechanism of methanol oxidation by quinoprotein methanol dehydrogenase (MDH.PQQ) in combination with methanol (MDH.PQQ.methanol) involves Glu-171--CO2(-) general base removal of the hydroxyl proton of methanol in concert with hydride equivalent transfer to the >C5=O quinone carbon of pyrroloquinoline quinone (PQQ) and rearrangement to hydroquinone (PQQH2) with release of formaldehyde. Molecular dynamics (MD) studies of the structures of MDH.PQQ.methanol in the presence of activator NH3 and inhibitor NH4(+) have been carried out. In the MD structure of MDH.PQQ.methanol.NH3, the hydrated NH3 resides at a distance of approximately 24 A away from methanol and the ortho-quinone portion of PQQ. As such, influence of NH3 on the oxidation reaction is not probable. We find that NH4(+) competes with the substrate by hydrogen-bonding to Glu-171CO2(-) such that the MDH.PQQ.methanol.NH4(+) complex is not reactive. Ammonia readily forms imines with quinone. Imines are present in solution as neutral (>C5=NH) and protonated (>C5=NH2(+)) species. MD simulations establish that the >C5=NH2(+) derivative of MDH.PQQ(NH2(+).methanol structure is unreactive because of the nonproductive means of methanol binding. The structure obtained by the MD simulations with the neutral >C5=NH imine of MDH.PQQ(NH).methanol structure is similar to the reactive MDH.PQQ.methanol complex. This active site geometry allows for catalysis of hydride equivalent transfer to the >C5=NH of PQQ(NH) by concerted Glu-171CO(2)(-) general-base removal of the H-OCH3 proton and Arg-324H+ general-acid proton transfer to the imine nitrogen. Enzyme-bound
机译：喹蛋白甲醇脱氢酶（MDH.PQQ）与甲醇（MDH.PQQ.methanol）结合作用的甲醇氧化机理涉及Glu-171--CO2（-）去除甲醇中羟基的质子，并与氢化物当量转移协同作用生成吡咯并喹啉醌（PQQ）的> C5 = O醌碳，并重排为氢醌（PQQH2），并释放甲醛。在活化剂NH3和抑制剂NH4（+）存在下，对MDH.PQQ。甲醇的结构进行了分子动力学（MD）研究。在MDH.PQQ.methanol.NH3的MD结构中，水合NH3与甲醇和PQQ的邻醌部分的距离约为24A。这样，NH 3对氧化反应的影响是不可能的。我们发现NH4（+）通过氢键结合到Glu-171CO2（-）与底物竞争，从而MDH.PQQ.methanol.NH4（+）络合物不具有反应性。氨容易与醌形成亚胺。亚胺以中性（> C5 = NH）和质子化（> C5 = NH2（+））的形式存在于溶液中。 MD模拟确定MDH.PQQ（NH2（+）。甲醇）的> C5 = NH2（+）衍生物由于甲醇的非生产性手段而没有反应性。MD模拟通过中性> C5 = NH所获得的结构MDH.PQQ（NH）。甲醇的亚胺结构类似于反应性MDH.PQQ。甲醇复合物，这种活性部位的几何形状可通过Glu-171CO催化氢化物当量转移至PQQ（NH）的> C5 = NH （2）（-）除去H-OCH3质子和Arg-324H +通用酸质子转移到亚胺氮上PQQ [PQQ（NH）]和CH的酶结合

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号