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钼辅因子酶 mARC:多功能酶还是杂化酶?

The molybdenum cofactor enzyme mARC: Moonlighting or promiscuous enzyme?

机构信息

Dpto. de Bioquímica y Biología Molecular, Campus de Rabanales y Campus Internacional de Excelencia Agroalimentario (CeiA3), Edif. Severo Ochoa, Universidad de Córdoba, Spain.

出版信息

Biofactors. 2017 Jul 8;43(4):486-494. doi: 10.1002/biof.1362. Epub 2017 May 12.

DOI:10.1002/biof.1362
PMID:28497908
Abstract

Molybdenum (Mo) is present in the active center of eukaryotic enzymes as a tricyclic pyranopterin chelate compound forming the Mo Cofactor (Moco). Four Moco containing enzymes are known in eukaryotes, nitrate reductase (NR), sulfite oxidase (SO), xanthine oxidoreductase (XOR), and aldehyde oxidase (AO). A fifth Moco enzyme has been recently identified. Because of the ability of this enzyme to convert by reduction several amidoximes prodrugs into their active amino forms, it was named mARC (mitochondrial Amidoxime Reducing Component). This enzyme is also able to catalyze the reduction of a broad range of N-hydroxylated compounds (NHC) as the base analogue 6-hydroxylaminopurine (HAP), as well as nitrite to nitric oxide (NO). All the mARC proteins need reducing power that is supplied by other proteins. The human and plants mARC proteins require a Cytochrome b5 (Cytb5) and a Cytochrome b5 reductase (Cytb5-R) to form an electron transfer chain from NADH to the NHC. Recently, plant mARC proteins were shown to be implicated in the reduction of nitrite to NO, and it was proposed that the electrons required for the reaction were supplied by NR instead of Cytochrome b5 components. This newly characterized mARC activity was termed NO Forming Nitrite Reductase (NOFNiR). Moonlighting proteins form a special class of multifunctional enzymes that can perform more than one function; if the extra function is not physiologically relevant, they are called promiscuous enzymes. In this review, we summarize the current knowledge on the mARC protein, and we propose that mARC is a new moonlighting enzyme. © 2017 BioFactors, 43(4):486-494, 2017.

摘要

钼(Mo)存在于真核酶的活性中心,作为三环吡喃并喋呤螯合物化合物形成钼辅因子(Moco)。在真核生物中已知有四种含有 Moco 的酶,硝酸盐还原酶(NR)、亚硫酸盐氧化酶(SO)、黄嘌呤氧化还原酶(XOR)和醛氧化酶(AO)。最近又鉴定出第五种 Moco 酶。由于该酶能够通过还原将几种酰胺肟前药转化为其活性氨基形式的能力,因此将其命名为 mARC(线粒体酰胺肟还原成分)。该酶还能够催化多种 N-羟基化化合物(NHC)的还原,如碱基类似物 6-羟基氨基嘌呤(HAP)以及亚硝酸盐转化为一氧化氮(NO)。所有的 mARC 蛋白都需要还原力,而还原力由其他蛋白质提供。人和植物的 mARC 蛋白需要细胞色素 b5(Cytb5)和细胞色素 b5 还原酶(Cytb5-R)来形成从 NADH 到 NHC 的电子转移链。最近,植物 mARC 蛋白被证明参与亚硝酸盐向 NO 的还原,并且提出反应所需的电子由 NR 而不是细胞色素 b5 成分提供。这种新表征的 mARC 活性被称为形成 NO 的亚硝酸盐还原酶(NOFNiR)。多功能蛋白形成了一类特殊的多功能酶,可以执行多种功能;如果额外的功能与生理无关,则它们被称为混杂酶。在这篇综述中,我们总结了 mARC 蛋白的最新知识,并提出 mARC 是一种新的多功能蛋白。

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