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.

journal_name

Chem Res Toxicol

authors

Shinyashiki M,Pan CJ,Switzer CH,Fukuto JM

doi

10.1021/tx010102i

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

1584-9

issue

12

eissn

0893-228X

issn

1520-5010

pii

tx010102i

journal_volume

14

pub_type

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