Crystal Structures of Substrate-Free and Retinoic Acid-Bound Cyanobacterial Cytochrome P450 CYP120A1

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• 作者：Karin K&#xfc ; hnel ; Na Ke ; Max J. Cryle ; Stephen G. Sligar ; Mary A. Schuler ; Ilme Schlichting
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：June 24, 2008
• 年：2008
• 卷：47
• 期：25
• 页码：6552 - 6559
• 全文大小：7399K
• 年卷期：v.47,no.25(June 24, 2008)
• ISSN：1520-4995

文摘

The crystal structures of substrate-free and all-trans-retinoic acid-bound CYP120A1 from Synechocystis sp. PCC 6803 were determined at 2.4 and 2.1 Å resolution, respectively, representing the first structural characterization of a cyanobacterial P450. Features of CYP120A1 not observed in other P450 structures include an aromatic ladder flanking the channel leading to the active site and a triple-glycine motif within SRS5. Using spectroscopic methods, CYP120A1 is shown to bind 13-cis-retinoic acid, 9-cis-retinoic acid, and retinal with high affinity and dissociation constants of less than 1 µM. Metabolism of retinoic acid by CYP120A1 suggests that CYP120A1 hydroxylates a variety of retinoid derivatives in vivo. On the basis of the retinoic acid-bound CYP120A1 crystal structure, we propose that either carbon 2 or the methyl groups (C16 or C17) of the β-ionone ring are modified by CYP120A1.