Mass spectrometry metal-protein complexes

M.M. (2001) Electrospray ionization mass spectrometry of oligonucleotide complexes with drugs, metals and proteins. Mass Spectrom. Rev., 20, 61-87 ... 

Another means of moving beyond pure protein preparations to high-throughput characterization of proteomes is to enrich for phosphopeptides from complex mixtures by metal affinity chromatography (Andersson and Porath, 1986). Using this method, protein mixtures are proteolyzed to create peptides and phosphorylated peptides are enriched by metal affinity chromatography and subsequently identified by mass spectrometry. This method is limited, however, because in many cases phosphopeptides absorb poorly or nonphosphorylated peptides absorb nonspecifically to the metal affinity resins (Ahn and Resing, 2001). 

Electrospray ionization has allowed the observation of a great number of non-covalent complexes protein-protein, protein-metal ion, protein-drug and protein-nucleic acid. About one-third of the proteins exist as multimeric forms. Mass spectrometry allows the study of their quaternary structure. This has been done for alcohol dehydrogenase (ADH) from horse liver and from yeast. The ESI spectra are displayed in Figure 8.22. The horse liver ADH is observed to be dimeric whereas that of yeast is tetrameric [131]. 

Collins, M.O. and Yu, L. et al. (2005b) Robust enrichment of phosphorylated species in complex mixtures by sequential protein and peptide metal-affinity chromatography and analysis by tandem mass spectrometry. Sci. STKE 2005,16. 

In the context of chemical speciation, a new hyphenated technique, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), in combination with gel electrophoresis, appears as an emerging and powerful tool for metal complexation studies of proteins, giving multielement information about metals bound to the previously separated metalloproteins. 

ESI is a soft ionization technique (in contrast to ICP) and can be used to produce primarily intact proton-ated molecular ions of peptides and proteins. This technique, in combination with MS or tandem mass spectrometry (MS/MS), has been investigated in the last years for the ionization of metal-containing species (including Cd species) to obtain precise information of molecular weights and structural characterization of such bioligands at trace levels in complex matrices. 

ESI has proven to be a most convenient means to transfer typical organometallics from solution to the gas phase, especially when the species of interest is present in the ionic form in solution. The first study of using ESI-MS for the analysis of ionic transition-metal complexes was made by Chait in 1994 [200], in which intact principal ions for ruthenium(II) dipyridyl complexes was observed. This represents the beginning of mass spectrometric characterization of known and defined solution-phase organometallic species [201-204]. Since its development, ESI-MS has been most elaborated for the ionization of large biomolecules such as proteins as a biochemical tool. However, when coupled with ion/molecule reactions and tandem mass spectrometry, ESI-MS is rapidly becoming the technique of choice for solution... 

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