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

被引：309

作者：

Bryk, R

Lima, CD

Erdjument-Bromage, H

Tempst, P

Nathan, C

机构：

[1] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA

[2] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA

[3] Sloan Kettering Inst, Prot Ctr, New York, NY 10021 USA

[4] Cornell Univ, Weill Grad Sch Med Sci, Program Immunol, New York, NY 10021 USA

[5] Cornell Univ, Weill Grad Sch Med Sci, Program Struct Biol, New York, NY 10021 USA

[6] Cornell Univ, Weill Grad Sch Med Sci, Program Mol Biol, New York, NY 10021 USA

来源：

SCIENCE | 2002年 / 295卷 / 5557期

关键词：

D O I：

10.1126/science.1067798

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1073 / 1077

页数：5

共 23 条

[1] Mycobacterium tuberculosis lipoamide dehydrogenase is encoded by Rv0462 and not by the lpdA or lpdB genes [J].