• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >An Investigation of the Distal Histidyl Hydrogen Bonds in Oxyhemoglobin: Effects of Temperature, pH, and Inositol Hexaphosphate
【24h】

An Investigation of the Distal Histidyl Hydrogen Bonds in Oxyhemoglobin: Effects of Temperature, pH, and Inositol Hexaphosphate

机译：氧合血红蛋白中远端组氨酸氢键的研究：温度，pH和肌醇六磷酸的影响

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

On the basis of X-ray crystal structures and electron paramagnetic resonance (EPR) measure-nments, it has been inferred that the O2 binding to hemoglobin is stabilized by the hydrogen bonds between thenoxygen ligands and the distal histidines. Our previous study by multinuclear nuclear magnetic resonancen(NMR) spectroscopy has provided the first direct evidence of such H-bonds in human normal adultnoxyhemoglobin (HbO2 A) in solution. Here, the NMR spectra of uniformly 15nN-labeled recombinant humannHb A (rHb A) and fivemutant rHbs in the oxy formhave been studied under various experimental conditionsnof pH and temperature and also in the presence of an organic phosphate, inositol hexaphosphate (IHP). Wenhave found significant effects of pH and temperature on the strength of the H-bond markers, i.e., the cross-npeaks for the side chains of the two distal histidyl residues, R58His and β63His, which form H-bonds with thenO2 ligands. At lower pH and/or higher temperature, the side chains of the distal histidines appear to be morenmobile, and the exchange with water molecules in the distal heme pockets is faster. These changes in thenstability of the H-bonds with pH and temperature are consistent with the changes in the O2 affinity of Hb as anfunction of pH and temperature and are clearly illustrated by our NMR experiments. Our NMR results havenalso confirmed that this H-bond in the β-chain is weaker than that in the R-chain and is more sensitive tonchanges in pHand temperature. IHP has only aminor effect on theseH-bondmarkers compared to the effectsnof pH and temperature. These H-bonds are sensitive to mutations in the distal heme pockets but not affectedndirectly by the mutations in the quaternary interfaces, i.e., R1β1 and/or R1β2 subunit interface. These findingsnprovide new insights regarding the roles of temperature, hydrogen ion, and organic phosphate in modulatingnthe structure and function of hemoglobin in solution.
机译：根据X射线晶体结构和电子顺磁共振（EPR）的测量，可以推断出氧与血红蛋白的结合是通过氧配体与远端组氨酸之间的氢键稳定的。我们先前通过多核核磁共振波谱（NMR）进行的研究提供了溶液中人类正常的成人氧合血红蛋白（HbO2 A）中此类H键的第一个直接证据。在此，已经在pH和温度的各种实验条件下以及在有机磷酸盐肌醇六磷酸（IHP）的存在下，研究了15nN标记的重组人Hb A（rHb A）和五突变体rHb在氧形式下的NMR光谱。 Wenhave发现pH和温度对氢键标记物的强度有显着影响，即两个远端组氨酸残基R58His和β63His的侧链的交叉峰，它们与thenO2配体形成H键。在较低的pH和/或较高的温度下，远端组氨酸的侧链似乎更具流动性，并且与远端血红素袋中的水分子的交换更快。 H键的稳定性随pH和温度的这些变化与Hb的O2亲和力随pH和温度的变化一致，这已通过我们的NMR实验清楚地说明。我们的NMR结果还证实，β链中的H键比R链中的H键弱，并且在pH和温度下更敏感。与pH和温度的影响相比，IHP仅对这些H键标记具有氨基作用。这些H键对远端血红素袋中的突变敏感，但不受四级界面即R1β1和/或R1β2亚基界面的突变的直接影响。这些发现为温度，氢离子和有机磷酸酯在调节溶液中血红蛋白的结构和功能方面的作用提供了新的见解。

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