Modeling the Interfacial Interactions between CrtS and CrtR from Xanthophyllomyces dendrorhous, a P450 System Involved in Astaxanthin Production
Modeling the Interfacial Interactions between CrtS and CrtR from Xanthophyllomyces dendrorhous, a P450 System Involved in Astaxanthin Production
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DOI：
10.1021/jf302287f
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发表时间：
2012-09-05
影响因子：
6.1
通讯作者：
Cifuentes, Victor
中科院分区：
文献类型：
--
作者：
Alcaino, Jennifer;Fuentealba, Matias;Cifuentes, Victor
树状叶黄酵母是虾青素的天然来源，虾青素是一种广泛用于食品工业的类胡萝卜素。在这种酵母中，虾青素是由细胞色素 P450 CrtS 从 β-胡萝卜素合成的，该细胞色素 P450 CrtS 依赖于 CrtR（四结构域细胞色素 P450 还原酶 (CPR)）。尽管酿酒酵母具有内源性 CPR (ScCPR)，但 CrtS 的表达不会导致虾青素的产生，除非它与 CrtR 共表达。假设 CrtS 可以与 CrtR 或 ScCPR 的 FMN 结合域（分别为 XdFMNbd 和 ScFMNbd）相互作用，这项工作的目的是通过蛋白质建模和短分子动力学模拟来确定这些替代复合物之间可能的相互作用差异。考虑到最近提出的哺乳动物 P450 的膜方向，我们的 CrtS CrtR。模型预测两个 N 末端都与膜平面相邻，从而允许它们锚定。与 CrtS 和 FMNbd 之间可能的界面相比，Xanthophyllomyces 系统似乎通过更多的盐桥来稳定。
Xanthophyllomyces dendrorhous is a natural source of astaxanthin, a carotenoid widely used in the food industry. In this yeast, astaxanthin is synthesized from beta-carotene by a cytochrome P450, CrtS, which depends on CrtR, the four domain cytochrome P450 reductase (CPR). Although Saccharomyces cerevisiae has an endogenous CPR (ScCPR), expression of CrtS does not result in astaxanthin production unless it is coexpressed with CrtR Assuming that CrtS could interact with the FMN-binding domain of either CrtR or ScCPR (XdFMNbd and ScFMNbd, respectively), the aim of this work was to identify possible interaction differences between these alternative complexes by protein modeling and short molecular dynamics simulations. Considering the recently proposed membrane orientation of a mammalian P450, our CrtS CrtR. model predicts that both N-terminal ends stand adjacent to the membrane plane, allowing their anchoring. Compared with the possible interface between CrtS and both FMNbd, the Xanthophyllomyces system appears to be stabilized by more saline bridges.