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SUMMARY:Computational redesign of native enzyme active sites - Per Junior 
 Greisen\, Technical University of Denmark
DTSTART:20111101T140000Z
DTEND:20111101T143000Z
UID:TALK34415@talks.cam.ac.uk
CONTACT:Daniel Cole
DESCRIPTION:The ability to redesign enzymes to catalyze non-cognate chemic
 al transformations would have wide-ranging applications. We have developed
  a computational method for repurposing the reactivity of active site func
 tional\ngroups of metalloenzymes to catalyze new reactions. Using this met
 hod\, we have engineered a zinc-containing murine adenosine deaminase to c
 atalyze the hydrolysis of a model organophosphate with a catalytic efficie
 ncy kcat/Km ~104 M^-1^ s^-1^ after directed evolution. In the high-resolut
 ion crystal structure of the enzyme\, all but one of the designed residues
  adopt the designed conformation. The designed enzyme efficiently catalyze
 d the hydrolysis of the RP-isomer of a coumarinyl analog of the nerve agen
 t cyclosarin\, and showed striking substrate selectivity for coumarinyl le
 aving-groups. Computational redesign of native enzyme active sites complem
 ents directed evolution methods and offers a general approach for explorin
 g their untapped catalytic\npotential for new reactivities.
LOCATION:TCM Seminar Room\, Cavendish Laboratory
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