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Travelling-wave ion mobility mass spectrometry exposes structure of gold fingers


Researchers from the Virginia Commonwealth University (VA, USA) have differentiated confomers of synthetic gold finger peptides using traveling wave ion mobility mass spectrometry.  In this study, published in Angewandte Chemie, researchers separated isomeric gold metalloproteins resulting from zinc displacement with gold metal ions from two parent zinc fingers, derived from the NCp7-F2 protein and finger 3 of the Sp1 transcription factor (Sp1-F3).

The utility of gold complexes as therapeutic agents for conditions such as rheumatoid arthritis has been documented in several studies, with many gold-containing drugs currently on the market. The mode of action of these drugs has been proposed through displacement of zinc ion in proteins containing zinc finger motifs with gold metal ions, resulting in a change of conformation in the protein.

“The zinc ions in zinc fingers bind to four sulfur or nitrogen atoms of the protein’s cysteine and histidine residues,” explained Nicholas Farrell, Virginia Commonwealth University (VA, USA). “Gold ions bind to just two amino acid fragments and change the conformation of the protein. The “gold fingers” are no longer able to bind to nucleic acids, which may be therapeutically useful.”

While metal ions can utilize a variety of potential binding sites, a single conformation is usually preferred by each metalloprotein. Previously, it has not been possible to identify the location of specific binding sites in a mixture of conformers. Two gold fingers have now been closely examined by Farrell and his team. Farrell explained that “replacing the zinc in zinc finger three of Sp1 transcription factor leads to only a single gold finger species.” Researchers also identified that this species has a linear Cys-Au-His bond.

With regards to the NCp7-F2 protein, a HIV nucleocapsid protein, which is crucial to the replication of the virus, “putting gold in the zinc finger two of the protein NCp7-F2, leads to three different gold finger species with linear Cys-Au-Cys motifs, one of which is clearly predominant,” explained Farrell.

With the use of traveling wave ion mobility mass spectrometry , the three conformational isomers of the gold-modified zinc finger derived from the NCp7-F2 protein were separated. The acquisition of a distinct product ion spectra for each conformation enabled the characterization of the binding site.

Closing statement? Farrell concluded: “Ion mobility mass spectrometry thus provides important information about the changes in geometry caused by the exchange of zinc in the zinc finger proteins, as well as the selectivity and reactivity of such reactions. This could be of benefit in the search for new metal-based antiviral and antitumor drugs.”

Sources: Du Z, de Paiva RE, Nelson K, Farrell NP. Diversity in gold finger structure elucidated by traveling-wave ion mobility mass spectrometry. Angew. Chem. Int. Ed. 56(16), 4464–4467 (2017);


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