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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Dr. Raul Perez-Jimenez, Columbia University
Single-molecule Mechanoenzymology
Enzymes are exceptional catalysts able to accelerate reaction rates by several orders of magnitude. Much is still unknown about how enzymes tune their chemical mechanisms to obtain high reaction rates and specificity. The mechanisms of numerous enzymatic reactions have been studied using protein biochemistry and structural biological techniques like X-ray crystallography and NMR. These studies have been crucial in identifying structural features and conformational changes necessary for the catalytic activity of enzymes. The recent advent of single-molecule techniques has opened up new possibilities for studying enzyme dynamics in solution at the à ngström scale, where rearrangements of the participating atoms necessary for catalysis can be observed. These new approaches generate data that combined with structural information as well as computational analysis, have the potential for providing a more complete view of enzyme dynamics. I will present the newly developed single molecule force-clamp spectroscopy techniques to investigate the chemical mechanisms of catalysis of thioredoxins, a broad class of enzymes that specialize in reducing disulfide bonds (1). In addition, I will present recent work combining force-clamp techniques with computational methodologies for ancestral sequence resurrection, to study the chemistry and evolution of ancient enzymes. Paleoenzymology has made it possible the study of primordial life through the properties of enzymes present in ancient organisms (2). This provides a unique opportunity to investigate the molecular evolution of enzymes and their relations with important biological and geological events in the past. Finally, I will introduce new research on the use of force-clamp to study the mechanochemical properties of CD4, a cell surface receptor that serves as primary receptor for HIV-1.
(1) Perez-Jimenez R, et al. Diversity of chemical mechanisms in thioredoxin catalysis revealed by single-molecule force spectroscopy (2009). Nat Struct Mol Biol, 16(8):890-6.
(2) Perez-Jimenez R, et al. Single-molecule paleoenzymology probes the chemistry of resurrected enzymes (2011). Nat Struct Mol Biol, 18(5):592-6
For more information contact Prof. Larry Bottomley (404-894-4014)/
