The crystal structure of mitochondrial cytochrome bc1 in complex with famoxadone:: The role of aromatic-aromatic interaction in inhibition
The crystal structure of mitochondrial cytochrome bc1 in complex with famoxadone:: The role of aromatic-aromatic interaction in inhibition
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DOI：
10.1021/bi026252p
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发表时间：
2002-10-01
期刊：
影响因子：
2.9
通讯作者：
Xia, D
中科院分区：
文献类型：
--
作者：
Gao, XG;Wen, XL;Xia, D
泛醌醇细胞色素C氧化还原酶（EC. 1.10.2.2，bcl）是细胞呼吸所必需的完整膜蛋白复合物。11-亚基线粒体bcl复合物的结构进行了测定，有和没有杀真菌剂恶唑菌酮。恶唑酮的特异性抑制是通过芳香族-芳香族相互作用的协调优化来实现的，其中恶唑酮和衬于通道结合口袋的残基中的构象重排产生模拟苯的晶格的芳香族-芳香族相互作用的网络。由先前诱变支持的深刻的芳香族-芳香族相互作用为疏水环境中的特异性蛋白质-配体相互作用提供了结构基础。巨大的构象变化，无论是在细胞色素。B和ISP亚基的通道蛋白复合物，赋予实验证据的功能作用的细胞色素B诱导的构象逮捕的ISP，并允许识别一个可能的intrasubunit信号转导途径，控制ISP的运动。这些结果支持的抑制机制，这是符合要求的ISP运动在电子转移的这种复杂的。
Ubiquinol cytochrome c oxido-reductase (EC. 1.10.2.2, bcl) is an integral membrane protein complex essential to cellular respiration. Structures of the 11-subunit mitochondrial bcl complex were determined with and without the fungicide famoxadone. Specific inhibition by famoxadone is achieved through a coordinated optimization of aromatic-aromatic interactions where conformational rearrangements in famoxadone and in residues lining the inhibitor-binding pocket produce a network of aromatic-aromatic interactions that mimic the crystal lattice of benzene. The profound aromatic-aromatic interactions as supported by prior mutagenesis provide a structural basis for specific protein-ligand interaction in a hydrophobic environment. Dramatic conformational changes, both in cyt. b and ISP subunits in the inhibitor-protein complex, confer experimental evidence for a functional role of cytochrome b in the induced conformational arrest of ISP and allow the identification of a possible intrasubunit signal transduction pathway that controls the movement of ISP. These results support an inhibitory mechanism that is consistent with the requirement for ISP movement in the electron transfer of this complex.