Inclusion of conserved buried water molecules in the model structure of rat submaxillary kallikrein

Abstract

A new approach to the molecular modelling of homologous serine proteases isadopted, by including a set of 21 buried waters known to be preserved inenzymes sharing the primary specificity of trypsin, in the homology modellingof rat submaxillary gland kallikrein. Buried waters – water moleculessequestered from bulk solvent within a protein matrix – appear to beintegral conserved components of all serine proteases of known structure andshould be incorporated into serine protease models built on the basis ofsequence/structural homology to this family. The absence of such waters mightinduce errors in a force field simulation, favouring the formation ofnonexistent hydrogen bonds and locally inaccurate structure. The kallikreinmodel refinement has led to the conclusion that an additional buried watershould be added to the original rigid matrix of 21 conserved water molecules.The structurally preserved protein cavities of such waters validate themodelled structure.