Work

Bond Bundle Analysis of Ketosteroid Isomerase

Year: 2022

Type: article

Abstract: Bond bundle analysis is used to investigate enzymatic catalysis in the ketosteroid isomerase (KSI) active site. We identify the unique bonding regions in five KSI systems, including those exposed to applied oriented electric fields and those with amino acid mutations, and calculate the precise redistribution of electron density that accompanies either enhancement or inhibition of KSI catalytic activity. In two examples—using direct inspection of bond bundle regional properties, and using correlations between those properties and reaction barrier height—we arrive at similar conclusions, that catalytic enhancement results from promoting electron density redistribution between bonds within the KSI-docked substrate molecule in a way that closely resembles our mechanistic understanding of the forward catalyzed reaction. The catalyzing charge redistribution between bond bundles is prevalent in KSI systems catalyzed via electric fields or via amino acid mutation, and are thus suggestive of a general catalytic role.

Source: The Journal of Physical Chemistry B

DOI: 10.1021/acs.jpcb.2c03638

Authors: Timothy R. Wilson, Amanda Morgenstern, Anastassia N. Alexandrova, M.E. Eberhart

Institutions: Colorado School of Mines, University of Colorado Colorado Springs, University of California, Los Angeles

Language: English

Topic: Advanced Chemical Physics Studies

Subfield: Atomic and Molecular Physics, and Optics

Field: Physics and Astronomy

Domain: Physical Sciences

Open Access status: green

Funders: National Science Foundation, Office of Naval Research, Division of Chemistry, Office of Naval Research Global

Awards: G2706758889, G3251079418, G3391951469, Quantifying and Designing for Electrostatic Preorganization in Enzymes, G8876996369