Studying ubiquitin-like proteins across the domains of life
Event details
Date | 03.12.2019 |
Hour | 16:15 › 17:30 |
Speaker | Prof. Champak Chatterjee, Department of Chemistry, University of Washington (USA) |
Location | |
Category | Conferences - Seminars |
The group of Champak Chatterjee has developed chemical probes and synthetic strategies to study two ubiquitin family proteins – the prokaryotic ubiquitin-like protein (Pup) in Mycobacterium tuberculosis, and the small ubiquitin-like modifier protein (SUMO) in humans. Chatterjee will present key insights on the mechanism of protein pupylation, that led him to the development of peptide inhibitors. He will also describe biochemical studies with chemically sumoylated histones and propose a model for gene regulation by SUMO.
Talk abstract
The prokaryotic ubiquitin-like protein (Pup) is found in the disease-causing bacterium Mycobacterium tuberculosis that infects about a third of the world’s population. Protein modification by Pup, called pupylation, is necessary for the persistence of tuberculosis infection. Hence, the enzymes associated with pupylation are potentially new targets in drug-resistant tuberculosis. Chatterjee lab has developed new chemical probes for mechanistic studies of the enzymes associated with protein pupylation. Key insights gained from biochemical studies with these probes, which led to the development of peptide inhibitors of protein pupylation will be presented.
In contrast with Pup, the small ubiquitin-like modifier protein, SUMO, is a human protein critical for gene regulation and repair. Lysine side-chain modification by SUMO is a conserved modification of many important nuclear proteins, such as transcription factors and histones. Chatterjee lab has developed facile chemical strategies to synthesize human proteins modified by SUMO. Champak Chatterjee will present results from biophysical and biochemical studies enabled by his synthesis, and propose a model for gene regulation by histone sumoylation.
About Champak Chatterjee
Champak received his B.Sc. in Chemistry (First Class) from the University of Bombay, and an M.Sc. in Organic Chemistry from I.I.T. Bombay (Institute Silver Medal), where he synthesized non-natural amino acids in the laboratory of Prof. Sambasivarao Kotha. Champak then moved to the U.S. and performed doctoral studies in the research group of Prof. Wilfred van der Donk at the University of Illinois at Urbana-Champaign. At Illinois, Champak studied the mechanism of biosynthesis of a class of ribosomally synthesized and post-translationally modified peptide antibiotics called lantibiotics or RiPPs. His post-doctoral work in Prof. Tom Muir’s laboratory at the Rockefeller University focused on understanding the mechanism by which ubiquitin stimulates histone methylation, and developing new methods for the site-specific modification of proteins.
Champak Chatterjee webpage
Major publications
- 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”, Am. Chem. Soc.2013.
- 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”, Nature Communications.
- Dhall, A.; Weller, C.E.; Chu, A.; Shelton, P.M.M.; Chatterjee, C., “Chemically sumoylated histone H4 stimulates intranucleosomal demethylation by the LSD1-CoREST complex”, ACS Chemical Biology.
- Stewart, M.D.; Zelin, E.; Dhall, A.; Walsh, T.; Upadhyay, E.; Corn, J.E.; Chatterjee, C.; King, M.-C.; Klevit, R.E., “BARD1 is necessary for ubiquitylation of nucleosomal histone H2A and for transcriptional regulation of estrogen metabolism genes”, Natl. Acad. Sci. U.S.A. 2018.
- Hsu, L.P.; Shi, H.; Leonen, C.L.; Kang, J.; Chatterjee, C.*; Zheng, N.*, “Structural basis of H2B ubiquitination-dependent H3K4 methylation by COMPASS”, Molecular Cell (*co-corresponding)
Practical information
- Expert
- Free
- This event is internal
Organizer
- NCCR Chemical Biology - Prof. Beat Fierz LCBM