PADlock Cryptanalysis: a Bayesian Approach to Identifying Trends in the PTM Deimination
Mentor 1
Jennifer Grant
Mentor 2
James Church
Location
Union Wisconsin Room
Start Date
24-4-2015 10:30 AM
End Date
24-4-2015 11:45 AM
Description
Cellular proteins are subject to the post-translational modification known as deimination in which the amino acid arginine is converted into citrulline. Deiminated proteins are widespread in disease states and thought to play a role in Rheumatoid Arthritis, Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease, and cancer. Unlike phosphorylation, substrate specificity of the peptidyl-arginine deiminase (PAD) family of enzymes, which are responsible for deimination, remains elusive and ill defined. Our objective was to identify patterns in the sequence primary and secondary structures, which may underpin this modification. We found that deiminated sequences were most likely to be categorized as having a disorganized secondary structure. We show trends in how the sequence primary structure influences the likelihood of deimination, such as a preference for nonpolar residues at position N2 in deiminated sequences. We identify regions of specificity preference within sequences, and observe similar and dissimilar preferences between the PAD enzymes.
PADlock Cryptanalysis: a Bayesian Approach to Identifying Trends in the PTM Deimination
Union Wisconsin Room
Cellular proteins are subject to the post-translational modification known as deimination in which the amino acid arginine is converted into citrulline. Deiminated proteins are widespread in disease states and thought to play a role in Rheumatoid Arthritis, Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease, and cancer. Unlike phosphorylation, substrate specificity of the peptidyl-arginine deiminase (PAD) family of enzymes, which are responsible for deimination, remains elusive and ill defined. Our objective was to identify patterns in the sequence primary and secondary structures, which may underpin this modification. We found that deiminated sequences were most likely to be categorized as having a disorganized secondary structure. We show trends in how the sequence primary structure influences the likelihood of deimination, such as a preference for nonpolar residues at position N2 in deiminated sequences. We identify regions of specificity preference within sequences, and observe similar and dissimilar preferences between the PAD enzymes.
