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Testing Electrostatic Complementarity in Enzyme Catalysis: Hydrogen Bonding in the Ketosteroid Isomerase Oxyanion Hole

Figure 8

1H NMR Downfield Chemical Shifts for Substituted Phenolates Bound to tKSI D40N

(A) Representative spectra, with phenol p Ka shown on the left. From top to bottom: free enzyme, 3,4-dinitrophenol, 3-fluoro-4-nitrophenol, 4-nitrophenol, 3-fluoro-5-trifluoromethylphenol, 3,4-dichlorophenol, and 3-iodophenol.

(B) Correlation between increasing phenolate p Ka and increasing chemical shift of observed downfield peaks. Circles are the two downfield peaks observed for phenolate binding. A linear fit gives slopes of 0.76 ± 0.06 and 0.50 ± 0.06 ppm/p Ka unit for the most downfield (blue) and the second-most downfield (red) peak, respectively. The square is the main downfield peak observed with the intermediate analog equilenin (p Ka = 9.7), for comparison.

Figure 8

doi: https://doi.org/10.1371/journal.pbio.0040099.g008