Pattern of occurrence and occupancy of carbonylation sites in proteins

Abstract

Proteins are targets for modification by reactive oxygen species, and carbonylation is an important irreversible modification that increases during oxidative stress. While information on protein carbonylation is accumulating, its pattern is not yet understood. We have made a meta-analysis of the available literature data (456 carbonylation sites on 208 proteins) to appreciate the nature of carbonylation sites in proteins. Of the carbonylated (Arg, Lys, Pro, and Thr - RKPT) amino acids, Lys is the most abundant, whereas Pro is the most susceptible and Thr is the least susceptible. The incidence of carbonylation is lower in the N-terminal part of the protein primary sequence. Although a significantly higher number of carbonylated sites occur in Arg-, Lys-, Pro- and Thr-rich regions of proteins, the hydropathy environment of carbonylated sites is not significantly different from potential carbonylation sites. Comparison of metal-catalyzed oxidation of two closely related proteins indicates that this type of carbonylation might not be very specific in proteins. Interestingly, carbonylated sites show a very strong tendency to cluster together in the protein primary sequence hinting at some sort of discerning mechanism. While some attributes of protein carbonylation appear to be random, further investigations are warranted to appreciate the deterministic nature of protein carbonylation sites.