How does the enzyme enolase enhance the acidity at the alpha carbon of 2-phospho-D-glycerate? Contributions by resonance and inductive effects

Eva Cutler, and Dr. Joel Karty, Department of Chemistry, Elon University, 50 Campus Drive, Elon, NC 27244

Enolase is a glycolytic enzyme that catalyzes the dehydration of 2-phospho-D-glycerate (2-PG) to produce phosphoenolpyruvate (PEP). A key step in that conversion is the deprotonation of the alpha carbon of 2-PG, which is a carboxylate anion (RCO2ˉ). Under non-enzymatic conditions, the alpha carbon of a carboxylate anion is not acidic. Enolase facilitates that deprotonation by coordinating two Mg2+ cofactors with the CO2ˉ portion of 2-PG, which dramatically enhances the alpha carbon’s acidity. This study aims to quantify the contributions by resonance and inductive effects toward that acidity enhancement by the Mg2+ cofactors. The quantification of resonance and inductive effects in this chemical system were determined using a computational research method called vinylogue extrapolation (VE) (J. Am. Chem. Soc., 2003, 125, 2797) via Gaussian software. The model system studied was HCO2ˉ • Mg2+. Calculations were carried out at the density functional theory (B3LYP) and MP2 levels of theory, both using the 6-311++G(d,p) basis set. The results indicate that the inductive effects appear to be the dominant contribution to making the alpha carbon acidic, accounting for approximately 90% of the acidity enhancement.

Additional Abstract Information

Presenter: Eva Cutler

Institution: Elon University

Type: Poster

Subject: Biochemistry

Status: Approved

Time and Location

Session: Poster 1
Date/Time: Mon 1:30pm-2:30pm
Session Number: 2157