分枝杆菌的代谢酶通过一种硫氧还蛋白样蛋白与抗氧化防御相关联。

Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.

作者信息

Bryk R, Lima C D, Erdjument-Bromage H, Tempst P, Nathan C

机构信息

Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.

出版信息

Science. 2002 Feb 8;295(5557):1073-7. doi: 10.1126/science.1067798. Epub 2002 Jan 17.

DOI:10.1126/science.1067798

PMID:11799204

Abstract

Mycobacterium tuberculosis (Mtb) mounts a stubborn defense against oxidative and nitrosative components of the immune response. Dihydrolipoamide dehydrogenase (Lpd) and dihydrolipoamide succinyltransferase (SucB) are components of alpha-ketoacid dehydrogenase complexes that are central to intermediary metabolism. We find that Lpd and SucB support Mtb's antioxidant defense. The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD. The 2.0 angstrom AhpD crystal structure reveals a thioredoxin-like active site that is responsive to lipoamide. We propose that Lpd, SucB (the only lipoyl protein detected in Mtb), AhpD, and AhpC together constitute a nicotinamide adenine dinucleotide (reduced)-dependent peroxidase and peroxynitrite reductase. AhpD thus represents a class of thioredoxin-like molecules that enables an antioxidant defense.

摘要

结核分枝杆菌（Mtb）对免疫反应中的氧化和亚硝化成分发起顽固防御。二氢硫辛酰胺脱氢酶（Lpd）和二氢硫辛酰胺琥珀酰转移酶（SucB）是α-酮酸脱氢酶复合物的组成部分，而这些复合物在中间代谢中至关重要。我们发现Lpd和SucB支持Mtb的抗氧化防御。过氧化物酶烷基过氧化氢还原酶（AhpC）通过衔接蛋白AhpD与Lpd和SucB相连。2.0埃的AhpD晶体结构揭示了一个对硫辛酰胺有反应的类硫氧还蛋白活性位点。我们提出，Lpd、SucB（在Mtb中检测到的唯一脂酰化蛋白）、AhpD和AhpC共同构成一种烟酰胺腺嘌呤二核苷酸（还原型）依赖性过氧化物酶和过氧亚硝酸盐还原酶。因此，AhpD代表一类能够实现抗氧化防御的类硫氧还蛋白分子。