Role of water molecules in the structure and function of aspartic proteinases

Abstract

The solvent structure in the crystals of ten aspartic proteinases has been analyzed to find the possible roles of conserved water molecules in their structure and activity. 17 waters have been identified which are common to at least eight of the ten examined enzyme structures. These include the catalytic water molecule, whose direct involvement in the mechanism of action of aspartic proteinases has been proposed previously. There appears to be at least one more functionally important water molecule strategically located to stabilize the flexible 'flap' region during substrate binding. Many other waters stabilize the structure, whilst a few have been found to maintain the active-site geometry required for the function of the enzyme. In particular, two waters related by the approximate molecular dyad are involved in the formation and preservation of a network of hydrogen bonds extending from the active site.