Biodiversity of the P450 catalytic cycle: yeast cytochrome b 5/NADH cytochrome b 5 reductase complex efficiently drives the entire sterol 14‐demethylation (CYP51) reaction

FEBS Letters

Kelly, Steven L.¹  Manning, Nigel J.²  Kaderbhai, Mustak A.¹  Lamb, David C.¹  Kelly, Diane E.¹ 

[1] Institute of Biological Sciences, University of Wales Aberystwyth, Aberystwyth SY23 3DA, UK;Chemical Pathology, Sheffield Childrens Hospital, Sheffield S10 2UH, UK

关键词: P450 catalytic cycle;    Cytochrome P450 reductase;    Yeast;    Candida albicans;   

DOI  :  10.1016/S0014-5793(99)01548-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The widely accepted catalytic cycle of cytochromes P450 (CYP) involves the electron transfer from NADPH cytochrome P450 reductase (CPR), with a potential for second electron donation from the microsomal cytochrome b ₅/NADH cytochrome b ₅ reductase system. The latter system only supported CYP reactions inefficiently. Using purified proteins including Candida albicans CYP51 and yeast NADPH cytochrome P450 reductase, cytochrome b ₅ and NADH cytochrome b ₅ reductase, we show here that fungal CYP51 mediated sterol 14α-demethylation can be wholly and efficiently supported by the cytochrome b ₅/NADH cytochrome b ₅ reductase electron transport system. This alternative catalytic cycle, where both the first and second electrons were donated via the NADH cytochrome b ₅ electron transport system, can account for the continued ergosterol production seen in yeast strains containing a disruption of the gene encoding CPR.

【 授权许可】

Unknown