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A structural basis for H-NOX signaling in Shewanella oneidensis by trapping a histidine kinase inhibitory conformation

Erbil, W. Kaya, Price, Mark S., Wemmer, David E., Marletta, Michael A.
Proceedings of the National Academy of Sciences of the United States of America 2009 v.106 no.47 pp. 19753-19760
Shewanella oneidensis, eukaryotic cells, guanylate cyclase, heme, histidine kinase, iron, mutants, nitric oxide, nuclear magnetic resonance spectroscopy, operon, oxygen, prokaryotic cells, proteins, signal transduction
Heme nitric oxide/oxygen (H-NOX) proteins are found in eukaryotes where they are typically part of a larger protein such as soluble guanylate cyclase and in prokaryotes where they are often found in operons with a histidine kinase, suggesting that H-NOX proteins serve as sensors for NO and O₂ in signaling pathways. The Fe(II)-NO complex of the H-NOX protein from Shewanella oneidensis inhibits the autophosphorylation of the operon-associated histidine kinase, whereas the ligand-free H-NOX has no effect on the kinase. NMR spectroscopy was used to determine the structures of the Fe(II)-CO complex of the S. oneidensis H-NOX and the Fe(II)-CO complex of the H103G H-NOX mutant as a mimic of the ligand-free and kinase-inhibitory Fe(II)-NO H-NOX, respectively. The results provide a molecular glimpse into the ligand-induced conformational changes that may underlie kinase inhibition and the subsequent control of downstream signaling.