title: Mechanisms of nitrogen oxide-mediated disruption of metalloprotein function: an examination of the copper-responsive yeast transcription factor Ace1.
abstract: Nitric oxide (NO) has been found to inhibit the copper-responsive yeast transcription factor Ace1 in an oxygen-dependent manner. However, the mechanism responsible for NO-dependent inhibition of Ace1 remains unestablished. In the present study, the chemical interaction of nitrogen oxide species with Ace1 was examined using a yeast reporter system. Exposure of yeast to various nitrogen oxides, under a variety of conditions, revealed that the oxygen-dependent inhibition of Ace1 is due to the reaction of NO with O(2). The nitrosating nitrogen oxide species N(2)O(3) is likely to be the disrupter of Ace1 activity. Considering the similarity of metal-thiolate ligation in Ace1 with other mammalian metalloproteins such as metallothionein, metal chaperones, and zinc-finger proteins, these results help to understand the biochemical interactions of NO with those mammalian metalloproteins.
authors.affiliation: Department of Pharmacology, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, California 90095-1735, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shinyashiki
authors.forename: C J
authors.initials: CJ
authors.lastname: Pan
authors.forename: C H
authors.initials: CH
authors.lastname: Switzer
authors.forename: J M
authors.initials: JM
authors.lastname: Fukuto
mesh_terms: D003300:Copper / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008667:Metalloproteins / Q000378:metabolism*; D009566:Nitrates / Q000633:toxicity; D009589:Nitrogen Oxides / Q000378:metabolism / Q000633:toxicity*; D010100:Oxygen / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C060256:CUP2 protein, S cerevisiae; D004268:DNA-Binding Proteins; D008667:Metalloproteins; D009566:Nitrates; D009589:Nitrogen Oxides; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C039642:peroxynitric acid; D003300:Copper; D010100:Oxygen