STRUCTURE OF CYTOCHROME P450 REDOX PARTNER COMPLEXES

P450酶与其氧化还原伙伴和 电子转移的机制是最重要和最耐人寻味的 P450研究领域的问题。四个化合物的晶体结构 细菌P450s，微粒体P450还原酶的催化域，以及 已知Putidaredosin的核磁共振结构。然而，了解这些知识 结构并不直接回答蛋白质在哪里以及如何相互作用。 由于结晶学中其他电子转移蛋白的相互作用 电子转移络合物被证明是特定的和相关的。 发生在溶液中，我们认为P450-氧化还原的结晶 合作伙伴复合体将能够识别相互作用地点， 结合时发生的构象变化，以及来自 一个因素影响另一个因素。P450cam电子转移系统和 黄细胞色素P450BM-3的血红素/FMN结合结构域 结构类似于微粒体P450和还原酶，是最好的 I级和II级结晶试验候选人 单加氧酶系统。 在结晶了共价连接的血红素/FMN结合结构域和 分离的血红素结合域和FMN结合域之间的非共价复合体 在P450BM-3中，我们处于一个很好的位置来解决这些结构， 这无疑将使我们更好地理解这一机制 以及微粒体P450依赖的单加氧酶系统的功能。

Interaction of the P450 enzymes with their redox partners and the mechanism of electron transfer are the most important and intriguing problems in the area of P450 research. The crystal structures of four bacterial P450s, the catalytical domain of microsomal P450 reductase, and the NMR structure of putidaredoxin are known. However, knowledge of these structures does not directly answer where and how the proteins interact. Since interaction of other electron transfer proteins in crystallographic electron transfer complexes was shown to be specific and relevant to that occurring in a solution, we propose that crystallization of P450-redox partner complexes will enable the identification of interaction sites, conformation changes occurring upon binding, and the electron pathway from one co-factor to another. The P450cam electron transfer system and the heme/FMN-binding domain of flavocytochrome P450BM-3, a functional and structural analog to microsomal P450s and reductase, are the best candidates for crystallization trials of Class I and Class II monooxygenase systems, respectively. Having crystallized both the covalently linked heme/FMN-binding domain and the non-covalent complex between the separate heme-and FMN-binding domains of P450BM-3, we are in an excellent position to solve these structures, which will, undoubtedly, lead to our better understanding of the mechanism and function of microsomal P450-dependent monooxygenase systems.