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Protection from nitrosative stress: a central role for microbial flavohemoglobin.
- Source :
-
Free radical biology & medicine [Free Radic Biol Med] 2012 May 01; Vol. 52 (9), pp. 1620-33. Date of Electronic Publication: 2012 Feb 06. - Publication Year :
- 2012
-
Abstract
- Nitric oxide (NO) is an inevitable product of life in an oxygen- and nitrogen-rich environment. This reactive diatomic molecule exhibits microbial cytotoxicity, in large part by facilitating nitrosative stress and inhibiting heme-containing proteins within the aerobic respiratory chain. Metabolism of NO is therefore essential for microbial life. In many bacteria, fungi, and protozoa, the evolutionarily ancient flavohemoglobin (flavoHb) converts NO and O(2) to inert nitrate (NO(3)(-)) and undergoes catalytic regeneration via flavin-dependent reduction. Since its identification, widespread efforts have characterized roles for flavoHb in microbial nitrosative stress protection. Subsequent genomic studies focused on flavoHb have elucidated the transcriptional machinery necessary for inducible NO protection, such as NsrR in Escherichia coli, as well as additional proteins that constitute a nitrosative stress protection program. As an alternative strategy, flavoHb has been heterologously employed in higher eukaryotic organisms such as plants and human tumors to probe the function(s) of endogenous NO signaling. Such an approach may also provide a therapeutic route to in vivo NO depletion. Here we focus on the molecular features of flavoHb, the hitherto characterized NO-sensitive transcriptional machinery responsible for its induction, the roles of flavoHb in resisting mammalian host defense systems, and heterologous applications of flavoHb in plant/mammalian systems (including human tumors), as well as unresolved questions surrounding this paradigmatic NO-consuming enzyme.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Aerobiosis
Amino Acid Sequence
Anaerobiosis
Dihydropteridine Reductase chemistry
Dihydropteridine Reductase genetics
Escherichia coli Proteins chemistry
Escherichia coli Proteins genetics
Gene Expression Regulation, Bacterial
Hemeproteins chemistry
Hemeproteins genetics
Humans
Molecular Sequence Data
NADH, NADPH Oxidoreductases chemistry
NADH, NADPH Oxidoreductases genetics
Nitric Oxide physiology
Protein Conformation
Sequence Homology, Amino Acid
Transcription, Genetic
Dihydropteridine Reductase physiology
Escherichia coli Proteins physiology
Hemeproteins physiology
NADH, NADPH Oxidoreductases physiology
Nitrosation
Oxidative Stress
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4596
- Volume :
- 52
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 22343413
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2012.01.028