Structure and conformational dynamics of the metalloregulator MerR upon binding of Hg(II).

The bacterial metalloregulator MerR is the index case of an eponymous family of regulatory proteins, which controls the transcription of a set of genes (the mer operon) conferring mercury resistance in many bacteria. Homodimeric MerR represses transcription in the absence of mercury and activates transcription upon Hg(II) binding. Here, the average structures of the apo and Hg(II)-bound forms of MerR in aqueous solution are examined using small-angle X-ray scattering, indicating an extended conformation of the metal-bound protein and revealing the existence of a novel compact conformation in the absence of Hg(II).

AGIX-4207 [2-[4-[[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]thio]-2,6-bis(1,1-dimethylethyl)phenoxy]acetic acid], a novel antioxidant and anti-inflammatory compound: cellular and biochemical characterization of antioxidant activity and inhibition of redox-sensitive inflammatory gene expression.

The pathogenesis of chronic inflammatory diseases, including rheumatoid arthritis, is regulated, at least in part, by modulation of oxidation-reduction (redox) homeostasis and the expression of redox-sensitive inflammatory genes including adhesion molecules, chemokines, and cytokines. AGIX-4207 [2-[4-[[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]thio]-2,6-bis(1,1-dimethylethyl)phenoxy]acetic acid] is a novel, orally active, phenolic antioxidant and anti-inflammatory compound with antirheumatic properties. To elucidate its anti-inflammatory mechanisms, we evaluated AGIX-4207 for a variety of cellular, biochemical, and molecular properties.