Structures of Silver Fingers and a Pathway to Their Genotoxicity

Recently, we demonstrated that Ag(I) can directly replace Zn(II) in zinc fingers (ZFs). The cooperative binding of Ag(I) to ZFs leads to a thermodynamically irreversible formation of silver clusters destroying the native ZF structure. Thus, a reported loss of biological function of ZF proteins is a likely consequence of such replacement. Here, we report an X‐ray absorption spectroscopy (XAS) study of Ag( n )S( n ) clusters formed in ZFs to probe their structural features. Selective probing of the local environment around Ag(I) by XAS showed the predominance of digonal Ag(I) coordination to two sulfur donors, coordinated with an average Ag−S distance at 2.41 Å. No Ag−N bonds were present. A mixed AgS(2)/AgS(3) geometry was found solely in the CCCH Ag(I)−ZF. We also show that cooperative replacement of Zn(II) ions with the studied Ag(2)S(2) clusters occurred in a three‐ZF transcription factor protein 1MEY#, leading to a dissociation of 1MEY# from the complex with its cognate DNA.