4.6 Article

Structural modeling of cytochrome P450 51 from a deep-sea fish points to a novel structural feature in other CYP51s

期刊

JOURNAL OF INORGANIC BIOCHEMISTRY
卷 245, 期 -, 页码 -

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2023.112241

关键词

Cytochrome P450; CYP51; Deep sea; Pressure; Adaptation; Fish

向作者/读者索取更多资源

This study investigates the molecular adaptation of deep-sea proteins to high hydrostatic pressure using cytochrome P450 enzymes from Coryphaenoides armatus. The results reveal the ability of Coryphaenoides armatus CYP51 enzyme to bind and catalyze the metabolism of its substrate, as well as amino acid substitutions and novel internal cavities that may be related to deep-sea adaptation. This research contributes to our understanding of protein functional adaptation in extreme environments.
Cytochromes P450 (CYP), enzymes involved in the metabolism of endogenous and xenobiotic substrates, provide an excellent model system to study how membrane proteins with unique functions have catalytically adapted through evolution. Molecular adaptation of deep-sea proteins to high hydrostatic pressure remains poorly un-derstood. Herein, we have characterized recombinant cytochrome P450 sterol 14 alpha-demethylase (CYP51), an essential enzyme of cholesterol biosynthesis, from an abyssal fish species, Coryphaenoides armatus. C. armatus CYP51 was heterologously expressed in Escherichia coli following N-terminal truncation and purified to homo-geneity. Recombinant C. armatus CYP51 bound its sterol substrate lanosterol giving a Type I binding spectra (KD 15 mu M) and catalyzed lanosterol 14 alpha-demethylation turnover at 5.8 nmol/min/nmol P450. C. armatus CYP51 also bound the azole antifungals ketoconazole (KD 0.12 mu M) and propiconazole (KD 0.54 mu M) as determined by Type II absorbance spectra. Comparison of C. armatus CYP51 primary sequence and modeled structures with other CYP51s identified amino acid substitutions that may confer an ability to function under pressures of the deep sea and revealed heretofore undescribed internal cavities in human and other non-deep sea CYP51s. The functional significance of these cavities is not known. Prologue: This paper is dedicated in memory of Michael Waterman and Tsuneo Omura, who as good friends and colleagues enriched our lives. They continue to inspire us.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据