Enzyme catalysis by hydrogen bonds: the balance between transition state binding and substrate binding in oxyanion holes.

Oxyanion holes stabilize oxygen anions in transition states. Data have been gathered both from enzyme structures and from corresponding structures from the Cambridge Crystallographic Database. The two data sets show a striking contrast. The small molecule interactions in the Cambridge database optimize hydrogen bonding. The enzyme active sites do not. Analyzing the data with the help of DFT calculations on theozyme-like models, we conclude that enzymes have not optimized binding to the transition state structures in reaction pathways involving oxyanion holes, because the best binding arrangement for the anions also optimizes binding for the starting materials of the reactions. Instead, enzymes arrange the hydrogen bonds so that the oxyanions are stabilized reasonably, but suboptimally, in order to avoid overstabilization of the ground state.