PubMed · 9385521
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K F Thomson, R Charles-Holmes, M H Beck. 1997. Primula dermatitis mimicking herpes simplex.. https://doi.org/10.1111/j.1600-0536.1997.tb00200.x
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Heat shock and other proteotoxic stresses cause accumulation of nonnative proteins that trigger activation of heat shock protein (Hsp) genes. A chaperone/Hsp functioning as repressor of heat shock transcription factor (HSF) could make activation of hsp genes dependent on protein unfolding. In a novel in vitro system, in which human HSF1 can be activated by nonnative protein, heat, and geldanamycin, addition of Hsp90 inhibits activation. Reduction of the level of Hsp90 but not of Hsp/c70, Hop, Hip, p23, CyP40, or Hsp40 dramatically activates HSF1. In vivo, geldanamycin activates HSF1 under conditions in which it is an Hsp90-specific reagent. Hsp90-containing HSF1 complex is present in the unstressed cell and dissociates during stress. We conclude that Hsp90, by itself and/or associated with multichaperone complexes, is a major repressor of HSF1.
The pH dependence of the redox potentials for the oxidized/reduced couples of methylamine dehydrogenase (MADH) and aromatic amine dehydrogenase (AADH) were determined. For each enzyme, a change of -30 mV/pH unit was observed, indicating that the two-electron transfer is linked to the transfer of a single proton. This result differs from what was obtained from redox studies of a tryptophan tryptophylquinone (TTQ) model compound for which the two-electron couple is linked to the transfer of two protons. This result also distinguishes the redox properties of the enzyme-bound TTQ from those of the membrane-bound quinone components of respiratory and photosynthetic electron transfer chains that transfer two protons per two electrons. This difference is attributed to the accessibility of TTQ to solvent in the enzymes. One of the quinol hydroxyls is shielded from solvent and thus is not protonated. The unusual property of TTQ enzymes of stabilizing the anionic form of the reduced quinol is important for the reaction mechanism of MADH because it allows stabilization of physiologically important reaction intermediates. Examination of the extent to which disproportionation of the MADH and AADH semiquinones occurred as a function of pH revealed that the equilibrium concentration of semiquinone increased with pH. This indicates that the proton transfer is linked to the semiquinone/quinol couple. Therefore, the quinol is singly protonated, and the semiquinone is unprotonated and anionic. It was also shown that the oxidation-reduction midpoint potential for AADH is 20 mV less positive than that of MADH over the range of pH values that was studied and that the TTQ semiquinone of AADH was less stable than that of MADH. This may be explained by differences in the active site environments of the two enzymes, which modulate their respective redox properties.
Cytochrome bo is a four-subunit terminal ubiquinol oxidase in the aerobic respiratory chain of Escherichia coli that vectorially translocates protons not only via directed protolytic reactions but also via proton pumping. Previously, we postulated that a bound quinone in the high-affinity quinone binding site (QH) mediates electron transfer from the low-affinity quinol oxidation site (QL) in subunit II to low-spin heme b in subunit I as an electron gate and a transient electron reservoir [Sato-Watanabe, M., Mogi, T., Ogura, T., Kitagawa, T., Miyoshi, H., Iwamura, H., and Anraku, Y. (1994b) J. Biol. Chem. 269, 28908-28912]. In the present study, we carried out screening of ubiquinone analogues using a bound ubiquinone-free enzyme (DeltaUbiA1) that has been isolated from a ubiquinone biosynthesis mutant, and identified PC24 (2-chloro-4, 6-dinitrophenol), PC32 (2,6-dibromo-4-cyanophenol), and PC52 (2-isopropyl-5-methyl-4,6-dinitrophenol) as potent QH site inhibitors. PC15 (2,6-dichloro-4-nitrophenol) and PC16 (2, 6-dichloro-4-dicyanovinylphenol), potent QL site inhibitors, did not exhibit such a selective inhibition of the QH site. Binding studies using the air-oxidized DeltaUbiA enzyme showed that PC32 and PC52 have 4- to 7-fold higher affinity than ubiquinone-1. Reconstitution of the QH site with PC32 and PC52 resulted in a decrease of the apparent Vmax value to 1/7 and 1/3, respectively, of the control activity. These findings suggest that structural features of the QL and QH sites are different, and provide further support for the involvement of the QH site in intramolecular electron transfer and facile oxidation of quinols at the QL site.