Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor.

Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Research Abstract Details 

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Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Abstract Text:

Ashwani Kumar,Jose C Toledo,Rakesh P Patel,Jack R Lancaster,Adrie J C Steyn,

A fundamental challenge to the study of oxidative stress responses of Mycobacterium tuberculosis (Mtb) is to understand how the protective host molecules are sensed and relayed to control bacilli gene expression. The genetic response of Mtb to hypoxia and NO is controlled by the sensor kinases DosS and DosT and the response regulator DosR through activation of the dormancy/NO (Dos) regulon. However, the regulatory ligands of DosS and DosT and the mechanism of signal sensing were unknown. Here, we show that both DosS and DosT bind heme as a prosthetic group and that DosS is rapidly autooxidized to attain the met (Fe3+) form, whereas DosT exists in the O2-bound (oxy) form. EPR and UV-visible spectroscopy analysis showed that O2, NO, and CO are ligands of DosS and DosT. Importantly, we demonstrate that the oxidation or ligation state of the heme iron modulates DosS and DosT autokinase activity and that ferrous DosS, and deoxy DosT, show significantly increased autokinase activity compared with met DosS and oxy DosT. Our data provide direct proof that DosS functions as a redox sensor, whereas DosT functions as a hypoxia sensor, and that O2, NO, and CO are modulatory ligands of DosS and DosT. Finally, we identified a third potential dormancy signal, CO, that induces the Mtb Dos regulon. We conclude that Mtb has evolved finely tuned redox and hypoxia-mediated sensing strategies for detecting O2, NO, and CO. Data presented here establish a paradigm for understanding the mechanism of bacilli persistence.

Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Publishing Authors By Initials

A Kumar,JC Toledo,RP Patel,JR Lancaster,AJ Steyn,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: cyclic nucleotide-regulated protein kinases: protamine kinase research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: cyclic nucleotide-regulated protein kinases: protamine kinase research

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Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 11568-73

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 3

MONTH: 07

YEAR: 2007

Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Keywords Mesh Terms:

KEYWORDS: Protamine Kinase

MESH TERMS: physiology

Chemical & Substance for Abstract: Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Information

Substance Name: Protamine Kinase

Registry Number: EC 2.7.1.70

Grant and Affiliation Information for Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor.

AFFILIATION: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL71189

ACRONYM: HL

MEDLINETA: Proc Natl Acad Sci U S A

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