Short hydrogen bonds in the catalytic mechanism of alcohol and lactate dehydrogenases

Abstract

The survey of crystallographic data from the Protein Data Bank for 63 enzyme complexes with substrates indicates the presence of many short hydrogen bonds in the active site of alcohol (EC 1.1.1.1) and lactate (EC 1.1.1.27) dehydrogenases, which are formed between the substrate, or substrate analog, and the acid-base catalyst in enzyme. In the case of alcohol dehydrogenase enzymes, the short hydrogen bonds are clustering in the active site exactly at the bond-breaking position between the substrate and the acid-base catalyst in enzyme, with the frequency of 70-100%. In lactate dehydrogenase enzymes, this frequency is much lower and amounts to 15-30%. This result strongly suggests that the active site of alcohol dehydrogenases is designed to bind the substrate by short hydrogen bonds exactly at the bond-breaking position.