Movement of charges during enzyme catalytic cycle may be due to conformational changes, or to fast electron or proton transfer, or to both events. In each case, entropy production can be calculated using Terrel L. Hill's method, if relevant microscopic rate constants are known. When ranked by their evolutionary distance from putative common ancestor, three β-lactamases considered in this study show correspondingly increased catalytic constant, catalytic efficiency, and overall entropy production. The acylation and deacylation steps with concomitant proton shuttles are the most important contributors to overall entropy production. The maximal entropy production requirement for the ES↔EP or EP↔E + P step leads to optimal rate constants, performance parameters, and entropy production values, which are close to those extracted from experiments and also rank in accordance with evolutionary distances. Concurrent maximization of entropy productions for both proton transfer steps revealed that evolvability potential of different β-lactamases is similarly high. These results may have implications in particular for latent potential of β-lactamases to evolve further and in general for selection of optimized enzymes through natural or directed evolution.
Keywords: Catalytic efficiency; Entropy production; Enzyme evolution; Optimal rate constants; Proton transfer steps; β-lactamases.
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