Moving Wave-Ion Mobility Mass Spectrometry Reveals Structures of Gold Fingers

American scientists have figure out gold fingers using mobility of ion and mass spectrometry. They recognized the precise gold binding sites.

Drugs comprising gold have been employed for years to treat numerous conditions that are life threatening and can result in severe circumstances. Such drugs have also been proven useful in treating ailments like HIV and cancer. One way through which the gold based drugs work is the reason that gold ions force zinc based ions to move out of zinc proteins.

Now scientists from America have identified ‘gold fingers’ with help of ion mobility mass spectrometry. “The zinc ions found in the zinc fingers bind to four nitrogen or sulphur atoms of the protein’s cysteine and histidine residues,” confirms Nicholas P. Farrell of Virginia Commonwealth University, Richmond, USA.

“Gold based ions link to just two amino acid fragments and alter the conformation of the protein. The ‘gold fingers’ are no longer able to link to nucleic acids that may be therapeutically useful.” Although, there are a range of potential linking sites for metal ions, each of metalloprotein usually prefers a single conformation. It was primarily not feasible to determine where the particular binding sites were a mixture of conformers.

Farrell and his group have now closely analysed two gold fingers. According to Farrell, “substituting the zinc in the zinc finger 3 of Sp1 transcription factor results in just a single gold finger species.” The scientists recognized this as having a linear Cys-Au-His bond. In the situation of the HIV nucleocapsid protein that plays a crucial role in the substitution of the virus, “placing gold in the zinc finger 2 of the protein results in three distinct gold finger species with linear Cys-Au-Cys motifs, one of which is mainly predominant.”

The scientist’s success stems from their use of a specific analytical technique known as travelling – wave ion mobility mass spectrometry. In this method, the molecules to be recognized are ionized and the ions are augmented by an electronic field in a gas. Collisions with the gas molecules cause the ions to be slowed. Big, voluminous molecules are slowed more than small, compact ones as they collide more frequently. This makes it feasible to separate and differentiate isomers as well, as although they have the similar mass, their distinct geometries lead to different mobility.

“In this method, we were able to recognize the particular binding sites and modes for the gold – modified zinc fingers NCp7-F2 and Sp1-F3,” says Farrell. “Mobility of ion mass spectrometry thus offers vital information about the changes in geometry resulted from the exchange of zinc in the zinc finger proteins as well as the reactivity and selectivity of such reactions.”