Lecture: Molecular features that make ancestral enzymes more promiscuous than modern enzymes
Speaker: Professor Romas Kazlauskas
Title: Molecular features that make ancestral enzymes more promiscuous than modern enzymes
Date & time: May 29, 11:00
Venue: Lunchroom on level 2 in Alfa building (SciLifeLab Stockholm)
Please confirm you attendance via the registration form.
The event is free of charge.
Evolutionary biologists hypothesize that ancestral enzymes were generalists; that is, that they catalyzed several different reactions. We have reconstructed ten ancestral hydroxynitrile lyases and esterases from ~100 million years ago. All ten enzymes fold and are catalytically active. Further, they catalyze more reactions than their modern descendants. These promiscuous enzymes can serve as starting points to evolve new enzymes for biocatalysis.
The ancestral enzymes differ from modern ones by ~50 amino acid substitutions, but only ~5 are within the active site. Making these five ancestral substitutions in the active site of modern enzymes does not create a promiscuous enzyme. Distant residues must contribute to the promiscuity. An x-ray crystal structure of one ancestral enzyme shows a slightly larger active site and a more flexible structure.
Romas Kazlauskas earned his Ph.D. in chemistry at MIT. After postdoctoral work at Harvard and industrial research at General Electric, he taught chemistry at McGill University (Montréal, Canada) and currently teaches biochemistry at the University of Minnesota (Twin Cities, USA). He has been a visiting professor in Germany, Sweden and South Korea. His favorite course is protein engineering for which he is currently writing a textbook.
SciLifeLab Host: Per-Olof Syrén
Image courtesy of University of Minnesota