Premium
Detection and localization of protein modifications by high resolution tandem mass spectrometry
Author(s) -
Meng Fanyu,
Forbes Andrew J.,
Miller Leah M.,
Kelleher Neil L.
Publication year - 2004
Publication title -
mass spectrometry reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 126
eISSN - 1098-2787
pISSN - 0277-7037
DOI - 10.1002/mas.20009
Subject(s) - chemistry , electron capture dissociation , tandem mass spectrometry , mass spectrometry , fourier transform ion cyclotron resonance , electrospray ionization , fragmentation (computing) , top down proteomics , protein mass spectrometry , chromatography , computer science , operating system
For interrogation of peptides with diverse modifications, no other instrument is as versatile as the Fourier‐transform mass spectrometer (FTMS). Particularly using electrospray ionization (ESI), many intact proteins and their proteolytic products harboring post‐translational and chemical modifications (PTMs) have been studied by high resolution tandem mass spectrometry (MS/MS). The widely touted analytical figures of merit for FTMS in fact have translated into clarity when analyzing PTMs from phosphorylations to disulfides, oxidations, methylations, acetylations, and even exotic PTMs found in the biosynthesis of antibiotics and other natural products. A top down approach to PTM detection and localization is proving extensible to an increasing variety of PTMs, some of which are stable to MS/MS at the protein level but unstable to amide bond cleavage by threshold dissociations at the level of small peptides <3 kDa. In contrast, MS/MS using electron capture dissociation (ECD) allows precise localization of even labile PTMs given enough sample and abundant molecular ions. Finally, this brief synopsis of recent literature highlights specific PTMs that perturb the protein backbone therefore altering MS/MS fragmentation patterns. Thus, FTMS will continue its expansion into more laboratories in part because of its ability to detect and deconvolute the regulatory mechanisms of biology written in the language of PTMs. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:126–134, 2005