Title | SEMINAR: Prof. Robert S. Phillips, Department of Chemistry, University of Georgia, Athens, Georgia, USA, entitled "Ground State Strain in Enzyme Catalysis: The Case of Tyrosine Phenol-lyase", on Wednesday, Oct 23, 2013 at 11:00 am, Building 4-150. | Body |
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Chemistry Department |
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Prof. Robert S. Phillips
Department of Chemistry
University of Georgia, Athens, Georgia, USA |
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Ground State Strain in Enzyme Catalysis: The Case of Tyrosine Phenol-lyase |
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The C-C lyases, TIL and TPL catalyze the reversible β-eliminations of indole and phenol, respectively, from L-tryptophan and L-tyrosine, and there are no chemical analogues of these enzymatic reactions. The mechanisms for TIL and TPL were proposed to occur in a stepwise fashion, via intermediates similar to those predicted for SE1 electrophilic aromatic substitution reactions of indole and phenol. However, primary and secondary deuterium isotope effects on the elimination of indole by TIL suggest that proton transfer to C3 of the indole is concerted with the C3-Cβ bond breakage. Recent crystal structures of Y71F and F448H TPL complexes with 3-F-L-Tyr show clear evidence for ground state strain, with the aromatic ring of the substrate bent 20º out of plane with the Cβ-Cγ bond. At present, Pauling transition state stabilization, not ground state strain, is believed to be the major factor in reducing activation free energy in enzymes. Our results show that ground state strain (destabilization) can also play a significant role in enzyme catalysis. Furthermore, if this mechanism is shown to be concerted, this would be the first proven example of an SE2 mechanism for C-C bond cleavage in an enzymatic reaction. |
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Wednesday
October 30, 2013
11:00 AM |
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Building 4 - 150 |
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There will be a get-together with Refreshments between 10:45-11:00 am in B4 - 150
Courtesy: SAICSC-ACS |
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Dr. Mohammad Nahid Siddiqui, Chair, Seminars and Social Activities Committee |
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