Home Health Analysis of Protein Post-Translational Modifications by Mass Spectrometry
PTM Repositories and Data Mining Tools
There are a number of online PTM repositories including PhosphoSitePlus , SysPTM 2.0 , PTMCode , and ProteomeScout . PTMCode indicates functional links between individual and multiple PTMs including acetylation and methylation . Another software, ProteomeScout, provides a compendium of public PTM data, including quantitative proteomics and details on functional annotation . These repositories aid design of follow-on experimental work and provide data for the development of in silico prediction tools.
Computational Prediction Tools for Acetylation and Methylation Sites
There has been a focus on the development and application of tools to predict acetylation and methylation sites to complement and extend analysis performed in vitro in a cost-effective manner. The challenges around site prediction have been outlined by review and evaluation of PMeS, PLMLA, MeMo, MASA, BPB-PPMS, MethK, and iMethyl-PseAAC using a common dataset of methylation sites . It was concluded that performance needs to be optimized and that it would be of benefit to adopt different feature information for methyl-arginine and methyl-lysine predictors . The PLMLA tool also predicts acetylation sites and has been compared with the LAceP, EnsemblePail, PHOSIDA, and PSKAcePred acetylation site prediction software . The comparison utilized information on 13,810 acetylation sites from 6388 proteins, which was obtained from SysPTM 2.0 and PhosphoSitePlus databases. LAceP performed best, employing a logistic regression method to integrate information on amino acid sequence adjacent to acetylated sites, physicochemical properties, and the transition probability of adjacent amino acids .
A comprehensive and comparative analysis of acetylation, methylation, ubiq- uitinylation, and SUMOylation has identified conserved amino acid sequence association with secondary structure . Information, combined with site specificity data for enzymes mediating addition and removal of acetyl and methyl groups, can benefit site prediction as has been demonstrated for lysine acetyltransferases . Chemoselective reactions provide an MS method for the experimental determination of acetyl and methyl transferase activities. Examples include alkynyl-acetyl-CoA and SAM analogs for bioorthogonal click chemistry analysis of proteins that are substrates for acetylation and methylation, respectively [128-130]. These complement other MS-based analyses (Table 4.2).
Table 4.2 Biochemical methods coupled to MS for analysis of protein acetylation and methylation.
Notes: Lysine acylations other than acetylation can be analyzed .
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