Structures of Silver Fingers and a Pathway to Their Genotoxicity

Abstract

Recently, we demonstrated that AgI can directly replace ZnII in zinc fingers (ZFs). The cooperative binding of AgI 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 AgnSn clusters formed in ZFs to probe their structural features. Selective probing of the local environment around AgI by XAS showed the predominance of digonal AgI coordination to two sulfur donors, coordinated with an average Ag−S distance at 2.41 Å. No Ag−N bonds were present. A mixed AgS2/AgS3 geometry was found solely in the CCCH AgI−ZF. We also show that cooperative replacement of ZnII ions with the studied Ag2S2 clusters occurred in a three-ZF transcription factor protein 1MEY#, leading to a dissociation of 1MEY# from the complex with its cognate DNA.