The Study Of Binding Model Of Some Commercial Fungicides With Mitochondrial Respiratory Chain Complex â…¡

The mitochondrial respiratory Complex Ⅱ (EC 1.3.5.1) or Succinate dehydrogenase (SDH), also known as Succinate:ubiquinone oxidoreductase (SQR), is a key integral membrane protein in the tricarboxylic acid cycle that catalyzes the oxidation of succinate to fumarate in the mitochondrial matrix as succinate dehydrogenase. This oxidation reaction is coupled to the reduction of ubiquinone to ubiquinol at the mitochondrial inner membrane as one part of the electron transport chain. It consists of four subunits: flavoprotein (FP, containing a covalent FAD cofactors)、iron-sulfur protein (IP, containing three iron-sulfur clusters) and two membrane-anchor proteins (large cytochrome b binding protein CybL and small cytochrome b binding protein CybS). The soluble heterodimer is made up of FP and IP, with succinate dehydrogenase activity; The membrane-anchor proteins (CybL and CybS) anchoring the complex to the inner membrane contain the quinone reductase activity. SQRI (succinate:ubiquinone oxidoreductase inhibitors) fungicides is through fully or partially occupy the substrate ubiquinone site, suppresses the electrons from the succinate to the ubiquinone, thereby blocking the energy metabolism of pathogenic bacteria, restrain the growth of the pathogen, lead to the death, finally achieve the goal of prevention and control of plant diseases. Therefore, SQR has been identified as a novel target of a large family of agricultural fungicides.SQRI fungicides contain amide bond in the molecular structure, can be roughly divided into three parts:the side chain sections, acid and amide bridge part. By now, there are eighteen commercial fungicides, and seven acid part have pyrazole. Now, the literature has been reported the pig heart SQR with TTFA and AA5, and avian heart SQR with commercial fungicide Carboxin crystal complex structure, including the TTFA and AA5 is SQR specificity inhibitors. But the way of the combination of other types of SQR fungicide and protein is unknown. This paper is on the basis of crystal structure apply the molecular docking, membrane dynamics and MM/PBS A method study the binding mode between commercial fungicide Carboxin and Thifluzamide combined with SQR. Through hydrogen bond distance monitor,we find that Carboxin and Thifluzamide carbonyl oxygen atoms make strong hydrogen bonding interaction with B_W173 and D_Y91, and the Thifluzamide with C_R46 formed two ions-Pi, this is also the main reason for the difference active. The information of these molecular level will provide theoretical guidance for the design of the SQR fungicides.