Structures of the cuprous-thiolate clusters of the Mac1 and Ace1 transcriptional activators.

Abstract:

:X-ray absorption spectroscopy on the minimal copper-regulatory domains of the two copper-regulated transcription factors (Ace1 and Mac1) in Saccharomyces cerevisiae revealed the presence of a remarkably similar polycopper cluster in both proteins. The Cu-regulatory switch motif of Mac1 consisting of the C-terminal first Cys-rich motif, designated the C1 domain, binds four Cu(I) ions as does the Cu-regulatory domain of Ace1. The four Cu(I) ions are bound to each molecule in trigonal geometry. An extended X-ray absorption fine structure (EXAFS) arising from outer-shell Cu...Cu interactions at 2.7 and 2.9 A was apparent in each Cu(I) complex indicative of a polycopper cluster. The intensity of the 2.9 A Cu...Cu backscatter peak, apparently diminished by partial cancellation, dominates the EXAFS. The results suggest that CuAce1 and CuMac1(C1) contain somewhat distorted forms of a known [Cu(4)-S(6)] cage in which a core of Cu atoms forming an approximate tetrahedron is bound by bridging thiolates above each of the six edges. The tetracopper clusters bound by Ace1 and Mac1 differ in that the Ace1 cluster is coordinated entirely by cysteinyl thiolate, whereas the cysteine-deficient Mac1 cluster appears to consist of a Cu(4)(S-Cys)(5)(N-His) cluster with a bridging histidyl-derived nitrogen.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Brown KR,Keller GL,Pickering IJ,Harris HH,George GN,Winge DR

doi

10.1021/bi0160664

subject

Has Abstract

pub_date

2002-05-21 00:00:00

pages

6469-76

issue

20

eissn

0006-2960

issn

1520-4995

pii

bi0160664

journal_volume

41

pub_type

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