Mechanistic impacts of post-translational modifications

Decidedly crucial chemical decoration

While DNA encodes our genetic blueprint, it is clear that much of the information that leads to precise biological outputs governing cell division, growth, differentiation and movement comes from chemical decoration of the genetic output known as protein post-translational modifications, or PTMs.

There are more than 200 distinct kinds of PTMs that are often reversible in nature but play key roles in health and disease. Much research now is dedicated to exploring the sites and extent of PTMs in the proteome; identifying the proteins that add, subtract and bind to these PTMs; understanding the precise functions of individual and clusters of PTMs; and investigating the potential for therapeutic interventions that inhibit disease-associated PTMs.

PTMs of lysine

Originally detected in our chromatin histone proteins, PTMs affecting lysine, including acetylation and methylation, are now understood to be widespread in the human proteome – with literally thousands of sites identified. This session will discuss emerging technologies that allow for the structural and functional analysis of protein lysine acetylation and methylation and the development of specific small-molecule therapeutic agents with anticancer potential that can target the enzymes that attach or remove these lysine PTMs.

PTMs of arginine

The sidechain guanidinium group of one or more arginines in a protein is often critical to that protein’s function, but PTMs can alter this, including methylation, phosphorylation and hydrolysis to citrulline. This session will touch on each of these arginine modifications and reveal new insights into the extent and function of these PTMs in biology and human disease.

PTMs of cysteine

Among the least abundant amino acids in proteins, cysteine residues are especially reactive both in nucleophilic and redox transformations, leading to a diverse array of PTMs. While undoubtedly important, many of these cysteine modifications are transient and difficult to characterize because of their instability. This session will discuss unraveling the biological pathways and functions of acyl and nitroso modifications on cysteine using a series of novel methods.


Reversible carbohydrate modification of cytosolic and nuclear proteins by N-acetyl-glucosamine on serine and threonine residues has become an exciting area of study in cell signaling. This session will discuss new functions of O-GlcNAcylation in health and disease and new insights into the complicated enzyme that catalyzes this PTM.

Philip Cole
Paul Thompson  
Organizers: Philip Cole, Johns Hopkins School of Medicine, and Paul R. Thompson, University of Massachusetts Medical School