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The overarching goal of my research program is to understand the system of inter- and intra-molecular interactions that dynamically regulate the catalytic mechanisms of enzymes to precisely time the events of the cell cycle. We employ a hybrid technological approach, including enzyme kinetics, mutagenesis, X-ray crystallography, NMR spectroscopy, and cryo-EM, to characterize these molecular machines. Our results provide mechanistic insight into the cell cycle that will influence the drug design of cancer therapeutics.

Animation: The interplay between APC/C, UBE2S, and UBE2C to ubiquitinate substrates during rapid cell cycle transitions.

In the video the gray blob with eyes is the APC/C. The car speeds along with the three protein complexes that are working together as fast as they can to reach the finish line and complete mitosis. ~Animation by Alejandro R. Martinez Chacin.

Martinez-Chacin RC et al. Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming. Nat Struct Mol Biol. 2020 Jun;27(6):550-560.