Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697-3900, USA.
Science. 2013 Jun 7;340(6137):1227-30. doi: 10.1126/science.1235797.
Cytochromes P450 catalyze a variety of monooxygenase reactions that require electron transfer from redox partners. Although the structure of many P450s and a small handful of redox partners are known, there is very little structural information available on redox complexes, thus leaving a gap in our understanding on the control of P450-redox partner interactions. We have solved the crystal structure of oxidized and reduced P450cam complexed with its redox partner, putidaredoxin (Pdx), to 2.2 and 2.09 angstroms, respectively. It was anticipated that Pdx would favor closed substrate-bound P450cam, which differs substantially from the open conformer, but instead we found that Pdx favors the open state. These new structures indicate that the effector role of Pdx is to shift P450cam toward the open conformation, which enables the establishment of a water-mediated H-bonded network, which is required for proton-coupled electron transfer.
细胞色素 P450 催化多种需要电子从氧化还原伴侣转移的单加氧酶反应。尽管许多 P450 和少数氧化还原伴侣的结构是已知的，但关于氧化还原复合物的结构信息非常有限，因此我们对 P450-氧化还原伴侣相互作用的控制理解存在差距。我们已经分别以 2.2 和 2.09 埃的分辨率解决了氧化和还原态 P450cam 与其氧化还原伴侣 putidaredoxin (Pdx) 复合物的晶体结构。预计 Pdx 将有利于封闭的底物结合 P450cam，这与开放构象有很大不同，但我们发现 Pdx 反而有利于开放状态。这些新结构表明，Pdx 的效应子作用是将 P450cam 推向开放构象，从而建立质子偶联电子转移所需的水介导氢键网络。
