Minkui Luo, from the Sloan-Kettering Cancer Center, will deliver a seminar entitled, "Interrogating Protein Methyltransferases with Cofactor Analogs." Hosted by Paramjit Arora.
For the speaker's research page, click here.
Protein methyltransferases (PMTs) play essential roles in many biological processes through methylation of histones and diverse nonhistone substrates. Dysregulation of these enzymes has been implicated in many diseases including cancers. It is challenging to dissect the methylomes of individual PMTs in an unambiguous manner because Lys/Arg methylation unlike other posttranslational modifications doesn’t significantly alter the physical property of the substrates. Pharmacological perturbation of these PMTs also requires high-quality inhibitors with distinct modes of action. To address these needs, we developed a set of cofactor-based chemical tools for PMTs. Our cofactor surrogates can be utilized wild-type and engineered PMTs for target labeling. This approach allows the identification of proteome-wide PMT substrates in an unbiased manner. Upon examining the catalytic mechanism of PMT-involved methylation reaction, we noticed the existence of dynamic configurations of PMTs, we were able to target these configurations and develop SAM-competitive inhibitors against certain PMTs. Under these contexts, several ongoing projects in the Luo laboratory will be presented.