Nitroxyl-mediated disruption of thiol proteins: inhibition of the yeast transcription factor Ace1.

Abstract:

:Among the biologically and pharmacologically relevant nitrogen oxides, nitroxyl (HNO) remains one of the most poorly studied and least understood. Several previous reports indicate that thiols may be a primary target for the biological actions of HNO. However, the intimate details of the chemical interaction of HNO with biological thiols remain unestablished. Due to their ability to grow under a variety of conditions, the yeast Saccharomyces cerevisiae represents a unique and useful model system for examining the chemistry of HNO with thiol proteins in a whole-cell preparation. Herein, we have examined the effect of HNO on the thiol-containing, metal-responsive, yeast transcription factor Ace1 under a variety of cellular conditions as a means of delineating the chemistry of HNO interactions with this representative thiol protein. Using a reporter gene system, we find that HNO efficiently inhibits copper-dependent Ace1 activity. Moreover, this inhibition appears to be a result of a direct interaction between Ace1 thiols and HNO and not a result of any chemistry associated with HNO-derived species. Thus, this report indicates that thiol proteins can be a primary target of HNO biochemistry and that HNO-mediated thiol modification is likely due to a direct reaction of HNO.

journal_name

Arch Biochem Biophys

authors

Cook NM,Shinyashiki M,Jackson MI,Leal FA,Fukuto JM

doi

10.1016/s0003-9861(02)00656-2

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

89-95

issue

1

eissn

0003-9861

issn

1096-0384

pii

S0003986102006562

journal_volume

410

pub_type

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