Biochemistry Seminar: P. Leslie Dutton, "Toward manmade light- and redox- driven oxidoreductases working in cells"
Mar 22, 2017
from 12:00 PM to 01:00 PM
|Where||CUNY ASRC Main Auditorium|
|Contact Name||Lauren Gohara|
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Bringing the idea of integrating de novo designed oxidoreductases and allied proteins into cell and organelle to replace or augment component parts of metabolic and bioenergetic machinery has some way to go to before benefit to mankind can be expected. Nevertheless, the challenge is worth taking on because once realized impact on creation in vivo of tailored solar and respiratory energy conversions, on chemical catalysis, on clinical/medical imaging /diagnostics, on control of photo- and oxidative damage and on remediating respiratory dysfunction of genetic or aging origins will be considerable.
We make use of a model maquette protein strategy that abstracts and transfers sufficiently understood functional elements drawn from complex multifunctional natural systems into elementary, structurally transparent de novo designed protein constructions where it is progressively developed and tailored for application.
Maquettes prove to be generally biocompatible: they can be equipped for structurally specific transport across membranes by the Tat or Sec translocons. Bacterial expression is coupled with biogenesis, programmed ligation and membrane transport of cofactors such as hemes B and C and bilins PCB and PEB; and we have indications of co-expressions/inclusion of carotenoids and chlorophyll. Maquettes promote diverse, relatively simple natural functions including light-capture and multistep energy-transfer and efficient charge-separation tuned to signaling and catalysis, diffusive inter-protein electron-transfer, and O2 ligation, stabilization and transport. Acquisition of high-resolution crystal structures of maquettes ligating multiple different cofactors familiar in photosynthesis and respiration is increasing design transparency.