Assistant Professor of Chemistry
Ph.D. University of Illinois at Urbana-Champaign, 2005
(Synthetic Protein Chemistry, Chemical Biology, Biochemistry)
Chemical approaches to study protein modifications
The complexity of cellular processes in higher organisms is in stark contrast with the relatively few protein-coding genes (~21,000) in their cells. The chemical modification of proteins after they are assembled on ribosomes, termed protein post-translational modification (PTM), is an important process that adds rich diversity to protein function. We are broadly interested in understanding how chemical modifications affect protein structure and function. Our specific focus is on studying protein modification by small ubiquitin-like proteins. We combine the powerful tools of synthetic organic chemistry and molecular biology to generate specifically modified proteins that are subjected to biochemical and biophysical investigation. Students in our group gain expertise in the synthesis, purification, and characterization of small molecules and proteins.
Two current areas of research are histone protein modification by the small ubiquitin-like protein modifier, SUMO, and modification of Mycobacterium tuberculosis proteins by the prokaryotic ubiquitin-like protein, Pup. We believe that understanding how these proteins modify the functions of their targets will allow us to devise new ways to control gene function and bacterial infection.
Shelton, P.; Weller, C.E.; Chatterjee, C. A facile N-mercaptoethoxyglycinamide (MEGA) linker approach to peptide thioesterification and cyclization. J. Am. Chem. Soc. 2017 (accepted).
Whedon, S.D.; Markandeya, N.; Rana, A.S.; Weller, C.E.; Senger, N.A.; Turecek, F.; Strieter, E.R.; Chatterjee, C. Selenocysteine as a latent bioorthogonal electrophilic probe for deubiquitylating enzymes. J. Am. Chem. Soc. 2016, 138, 13774–13777.
Weller, C.E.; Dhall, A.; Ding, F.; Linares, E.; Whedon, S.D.; Senger, N.A.; Tyson, E.L.; Bagert, J.D.; Li, X.; Augusto, O.; Chatterjee, C. Aromatic thiol-mediated cleavage of N-O bonds enables chemical ubiquitylation of folded proteins.
Nat Commun. 2016, 7, 12979.
Dhall, A.; Wei, S.; Fierz, B.; Woodcock, C.L.; Lee, T.H.; Chatterjee, C. Sumoylated human histone H4 prevents chromatin compaction by inhibiting long-range internucleosomal interactions. J. Biol. Chem. 2014, 289, 33827–33837.
Smirnov, D.; Dhall, A.; Sivanesam, K.; Sharar, R.J.; Chatterjee, C.
Fluorescent probes reveal a minimal ligase recognition motif in the prokaryotic ubiquitin like protein from Mycobacterium tuberculosis. J. Am. Chem. Soc. 2013, 135, 2887–2890.
Meier, F.; Abeywardana, T.; Dhall, A.; Marotta, N.P.; Varkey, J.; Langen, R.; Chatterjee, C.; Pratt, M. R. Semisynthetic, Site-Specific Ubiquitin Modification of α-Synuclein Reveals Differential Effects on Aggregation. J. Am. Chem. Soc. 2012, 134, 5468–5471.
Dhall, A.; Chatterjee, C. Chemical approaches to understand the language of histone modifications. ACS Chem. Biol. 2011, 6, 987–999.