Vibrational Stark Effects of Carbonyl Probes Applied to Reinterpret IR and Raman Data for Enzyme Inhibitors in Terms of Electric Fields at the Active Site

• DOI: 10.1021/acs.jpcb.6b08133
• Publication Date: 2016-08-19T21:54:23Z
• Authors: Samuel H. Schneider; Steven G. Boxer
• Keywords: Ketosteroid; Solvatochromism

IR and Raman frequency shifts have been reported for numerous probes of enzyme transition states, leading to diverse interpretations. In the case model ketosteroid isomerase (KSI), we argued that spectral a carbonyl probe at active site can provide connection between electric field activation free energy (Fried et al. Science 2014, 346, 1510–1514). Here generalize this approach much broader set (e.g., oxoesters, thioesters, amides), first establishing sensitivity each an using vibrational Stark spectroscopy, solvatochromism, MD simulations, then applying these results reinterpret data already in literature enzymes such as 4-chlorobenzoyl-CoA dehalogenase serine proteases. These demonstrate effect provides general framework estimating electrostatic contribution catalytic rate may metric design or modification enzymes. Opportunities limitations are also described.