Gregory A. Weiss, from the University of California at Irvine, will deliver a seminar entitled, "Making Enzymes Sing and Dance to Uncover Mechanistic Insights and New Therapeutics." Hosted by Paramjit Arora.
Zoom Link: https://nyu.zoom.us/j/97168147077
For more information about Greg Weiss, click here.
Abstract: This talk will describe dissecting and enhancing the function of ultra-
specific enzymes – Taq DNA polymerase and the protease used in Botox. With
collaborator Prof. Phil Collins (UCI), we have spot-welded individual proteins into
nanometer-scale electronic circuits, termed “nanophones,” to record the sounds
made by proteins in motion. The tethered single molecule can be examined at
high-speeds (microsecond resolution) for long durations (up to weeks) in real-
time during enzymatic catalysis. The approach has been used to dissect the
inner workings of several enzymes, including DNA polymerases and
protein kinase A. Recently, we have used these nanocircuits to examine the PCR
enzyme, Taq DNA polymerase. This enzyme functions at elevated temperatures
with fast conformational dynamics, which challenge conventional single molecule
studies. The rates and durations of the enzyme closing and its bond forming,
catalytic events had almost no temperature dependence, leaving Taq’s
temperature sensitivity to its rate-determining open state. We next turned
attention to the grand champion of specific enzymes, Botox protease (botulinum
neurotoxin serotype A, BoNT/A), which cuts a single amide bond in the human
proteome. Eight rounds of directed evolution uncovered insights into its
specificity and yielded a new potential therapeutic. In brief, both Taq and BoNT/A
protease achieve their vaunted catalytic specificity through binding to their
substrates in precatalytic steps.