Water as an Essential Cofactor for All Enzymes

Abstract

Enzymes are essential for the chemical reactions of all living organisms. Water is widely acknowledged as being important to enzyme action, but at the same time, a common textbook attribute of enzymes is that they protect the active site from water. We propose here that a more precise statement is that the universal function of enzymes is to provide a pathway for water to the active site, where it is activated. We further propose that this is true for all enzymes. This is to say that water is an essential co-factor for all enzymes, much like Mg2+ ion is for ATPase action. Herein we support this point of view with: (1) a survey of 55 crystal structures of enzymes arbitrarily chosen from all 6 classes of enzymes, all of which present a “water wire” leading from bulk water to the active site; (2) a survey of electric fields in nucleic acid transferases and hydrolases along water O-H bonds (in the presence and absence of substrate) that generally reveals much higher fields for water trapped near enzyme active sites in the presence of substrate; (3) a survey of electric fields on the ribose O2’-H2’ bonds that reveals a larger electric field on the nucleotides bond to be cleaved.