Bak Daniel W, Zuris John A, Paddock Mark L, Jennings Patricia A, Elliott Sean J
Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.
Biochemistry. 2009 Nov 3;48(43):10193-5. doi: 10.1021/bi9016445.
MitoNEET is a small mitochondrial protein that has been identified recently as a target for the thiazolidinedione (TZD) class of diabetes drugs. MitoNEET also binds a unique three-Cys- and one-His-ligated [corrected] [2Fe-2S] cluster. Here we use protein film voltammetry (PFV) as a means to probe the redox properties of mitoNEET and demonstrate the direct impact of TZD drug binding upon the redox chemistry of the FeS cluster. When TZDs bind, the midpoint potential at pH 7 is lowered by more than 100 mV, shifting from approximately 0 to -100 mV. In contrast, a His87Cys mutant negates the ability of TZDs to affect the midpoint potential, suggesting a model of drug binding in which His87 is critical to communication with the FeS center of mitoNEET.
线粒体硫氧还蛋白(MitoNEET)是一种小型线粒体蛋白,最近被确定为噻唑烷二酮(TZD)类糖尿病药物的作用靶点。MitoNEET还结合一个独特的由三个半胱氨酸和一个组氨酸配位的[校正后] [2Fe-2S]簇。在此,我们使用蛋白质膜伏安法(PFV)来探究MitoNEET的氧化还原特性,并证明TZD药物结合对FeS簇氧化还原化学的直接影响。当TZD结合时,pH 7时的中点电位降低超过100 mV,从约0 mV变为 -100 mV。相比之下,His87Cys突变体使TZD影响中点电位的能力丧失,这表明药物结合模型中His87对于与MitoNEET的FeS中心进行通信至关重要。