Flexibility of the CueR Metal Site Probed by Instantaneous Change of Element and Oxidation State from AgI to CdII. Issue 33 (19th May 2020)

• Record Type: Journal Article
• Authors: Balogh, Ria K.; Gyurcsik, Béla; Jensen, Mikael; Thulstrup, Peter W.; Köster, Ulli; Christensen, Niels Johan; Mørch, Frederik J.; Jensen, Marianne L.; Jancsó, Attila; Hemmingsen, Lars
• Is Part Of: Chemistry. Volume 26:Issue 33(2020)
• Page Start: 7451
• Page End: 7457
• Publication Date: 2020-05-19
• Subjects: cadmium -- flexibility -- protein function -- protein metal sites -- relaxation -- silver; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202000132
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Selectivity for monovalent metal ions is an important facet of the function of the metalloregulatory protein CueR. 111 Ag perturbed angular correlation of γ‐rays (PAC) spectroscopy probes the metal site structure and the relaxation accompanying the instantaneous change from Ag I to Cd II upon 111 Ag radioactive decay. That is, a change from Ag I, which activates transcription, to Cd II, which does not. In the frozen state (−196 °C) two nuclear quadrupole interactions (NQIs) are observed; one (NQI1 ) agrees well with two coordinating thiolates and an additional longer contact to the S77 backbone carbonyl, and the other (NQI2 ) reflects that Cd II has attracted additional ligand(s). At 1 °C only NQI2 is observed, demonstrating that relaxation to this structure occurs within ≈10 ns of the decay of 111 Ag. Thus, transformation from Ag I to Cd II rapidly disrupts the functional linear bis(thiolato)Ag I metal site structure. This inherent metal site flexibility may be central to CueR function, leading to remodelling into a non‐functional structure upon binding of non‐cognate metal ions. In a broader perspective, 111 Ag PAC spectroscopy may be applied to probe the flexibility of protein metal sites. Abstract : Relax : Ag I activates the transcriptional regulatory protein CueR, while Cd II does not activate CueR. In this work the fact that 111 Ag decays to 111 Cd is exploited, to elucidate the subsequent relaxation at the metal site from transcriptional activator to repressor by PAC spectroscopy. Considerable metal site flexibility is observed, and it is hypothesized that this is relevant to the function of CueR.