Crystal structures of the CO and NO Bound DosS GAF-A domain and implications for DosS signaling in Mycobacterium tuberculosis
| Autor: | Christopher A. Waddling, Paul R. Ortiz de Montellano, Yarrow Madrona |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Hemeprotein Stereochemistry Iron Biophysics Heme Protamine Kinase Crystal structure Crystallography X-Ray Nitric Oxide Biochemistry Redox Catalysis Protein Structure Secondary Article Ferrous 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Protein Domains medicine Amino Acids Phosphorylation Molecular Biology Dynamic equilibrium Carbon Monoxide 030102 biochemistry & molecular biology Autophosphorylation Hydrogen Bonding Mycobacterium tuberculosis Oxygen Crystallography 030104 developmental biology chemistry Ferric Protein Multimerization Oxidation-Reduction Signal Transduction medicine.drug |
| Zdroj: | Archives of Biochemistry and Biophysics. 612:1-8 |
| ISSN: | 0003-9861 |
| Popis: | DosS is a sensor in Mycobacterium tuberculosis that differentially responds to O2, NO, and CO, as well as to changes in the redox state of the prosthetic heme iron atom. The ferrous protein and its Fe(II)-NO and Fe(II)-CO complexes undergo autophosphorylation and subsequently transfer the phosphate group to DosR, a nuclear factor, to activate it. In contrast, autophosphorylation is negligible with the ferric protein and the Fe(II)-O2 complex. To clarify the basis for this differential response to gases, we have determined the crystal structures of the NO- and CO-complexes of the DosS GAF-A domain, which contains the heme to which the gases bind. Comparison of these crystal structures with those reported for the phosphorylation-inactive ferric GAF-A domain suggest that the GAF-A domain is in a dynamic equilibrium between active and inactive states, and that the position of Glu87 in the heme cavity, which depends on the which gas is bound, acts as a modulator of the equilibrium, and therefore of catalytic activity. |
| Databáze: | OpenAIRE |
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