肌红蛋白与H2S反应的结构功能学研究

近年来,内源性H_2S作为第3种被发现的新型气体信号分子,其生理学作用逐渐受到研究者的重视.在哺乳动物体内,H_2S与血红素蛋白的结合有两种方式,一种是H_2S直接键合血红素中心Fe形成Fe-H_2S复合物;另一种则是H_2S修饰血红素卟啉环,形成硫代血红素结构.我们选用肌红蛋白(myoglobin,Mb)作为研究对象,通过点突变技术改变了血红素活性中心结构,结合紫外-可见光谱学以及X-射线晶体学,研究了H_2S与不同突变型Mb反应后的光谱和结构变化.结果显示:血红素中心近、远端腔微环境的变化,如腔体极性、氢键数目、氢键位置等因素直接影响蛋白质与H_2S的结合,以及硫代血红素(sulfheme)的形成.这些结果为研究血红素蛋白参与内源性H_2S代谢机理提供了重要的实验数据.

Structure-function Studies of The Interactions of H2S With Myoglobin Mutants

Endogenous H₂S was recognized recently as a new gaseous signaling molecule which plays beneficial roles in vasodilation and facilitation of long-term potentiation. The interaction of mammalian myoglobin (Mb) with H₂S occurs via two distinct pathways: the first is the direct binding of H₂S to the heme-Fe center of the Mb to form the Mb-H₂S adduct, and the second is the covalent modification with H₂S at a porphyrin vinyl group of the Mb heme to form the covalently modified sulfheme. We chose Mb as the prototype heme-containing protein and probed the interactions of different Mb mutants with H₂S by UV-vis spectroscopy, and X-ray crystallography. The heme active sites of Mb mutants directly affect the binding of H₂S to the proteins and alsothe formation of sulfheme derivatives. This provides critical experimental data for elucidating how heme-containing proteins modify the metabolism of endogenous H₂S.