Structures of Silver Fingers and a Pathway to Their Genotoxicity
Katarzyna Kluska, Giulia Veronesi, Aurélien Deniaud, Bálint Hajdu, Béla Gyurcsik, Wojciech Bal, Artur Krężel
Abstract
Abstract 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.