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<p class="MsoNormal">Please join us today, Tuesday, April 11 for the 2017 Lord Lecture, part of the Modern Optics and Spectroscopy seminar. This year’s speaker will be
<b>Professor Steven G. Boxer</b> of Stanford University, presenting his talk on <b>
“Vibrational Stark Spectroscopy Connects Electrostatics to Catalytic Rates at Enzyme Active Sites.”</b> The talk will be held at 12pm in MIT 34-401, with lunch served immediately following the lecture.<o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:11.0pt">Abstract: <br>
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Electrostatic interactions impact every aspect of the structure and function of proteins, nucleic acids, and membranes, and this extends to any organized material. We have recently focused on the contribution of electric fields at the enzyme active site to
enzymatic catalysis. The transition states for many enzyme-catalyzed reactions involve a change in the distribution of charge relative to the starting material and/or products, and the selective stabilization of charge-separated transition states may be essential
for catalysis. The magnitudes of the electric fields in proteins and the variations in these fields at different sites are predicted to be enormous, but it is a challenge to obtain quantitative experimental information on these fields. We have developed vibrational
Stark spectroscopy to probe electrostatics and dynamics in organized systems, in particular in proteins where they can report on functionally important electric fields. The strategy involves deploying site-specific vibrational probes whose sensitivity to an
electric field is measured in a calibrated external electric field by vibrational Stark spectroscopy. This gives the magnitude of the vibrational frequency shift associated with an electric field change in a protein, e.g. by making a mutation, changing pH,
ligand binding, etc., projected along the bond axis, which is typically determined by x-ray crystallography. By measuring vibrational solvatochromism in conjunction with simulations and the vibrational Stark effect, we can obtain information on absolute fields,
and this can be applied to obtain information on functionally relevant electric fields at the active site of enzymes. Using ketosteroid isomerase as a model system, we correlate the field sensed at the bond involved in enzymatic catalysis with the rate of
the reaction it catalyzes, including variations in this rate in a series of mutants and variants prepared using non-canonical amino acids. This provides the first direct connection between electric fields and function: for this system electrostatic interactions
are a dominant contribution to catalytic proficiency. Tests of the approximations that go into this approach and extensions and generalizations to other enzymes, non-biological catalysts and problems in the condensed phase will be discussed.</span><o:p></o:p></p>
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<p class="MsoNormal"><b><span style="font-size:10.5pt;font-family:Tahoma;color:black">Christine Brooks</span></b><o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:10.5pt;color:black">Administrative Assistant</span><o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:10.5pt;color:black">Massachusetts Institute of Technology</span><o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:10.5pt;color:black">Department of Chemistry</span><o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:10.5pt;color:black">77 Massachusetts Ave, 6-333</span><o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:10.5pt;color:black">Cambridge, MA 02139</span><o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:10.5pt;color:black">p: 617.253.7239</span><o:p></o:p></p>
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<p class="MsoNormal"><span style="font-size:10.5pt;color:black">e: cbrooks@mit.edu</span><o:p></o:p></p>
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