Identification of novel ADP ribosylation sites in Mycobacterium tuberculosis isocitrate lyase by mass spectrometry

Abstract

Mass spectrometry is a powerful proteomics tool for the identification of therapeutic targets and disease biomarkers on one hand and for characterization of post-translationally modified (PTM) and alternatively spliced protein isoforms on the other. PTMs are the covalent modifications of certain proteins either by the addition of functional groups or by proteolytic cleavage. These modifications result in the structure-function regulations of target proteins and generate protein isoforms which may be associated with a particular disease. The prior knowledge of PTMs in a specific drug target aid in designing novel therapeutics. Isocitrate lyase (ICL) of Mycobacterium tuberculosis (Mtb) is one such drug target, which exists in two isoforms - ICL1 (Rv0467) and ICL2 (Rv1915 and Rv1916) and the activity of the former was reported to be regulated by lysine acetylation and succinylation. While reviewing the major PTMs in Mtb, this review also brings up the plausible role of reversible post-translational modifications such as ADP-ribosylation and acetylation Rv1915 and Rv1916 in assisting persistent Mtb to survive and respond to environmental cues respectively.