HisH+-His reactive sites in catalytic four-helix bundle catalysts

Abstract

Helix-loop-helix motifs with 42 amino acid residues that dimerize to four-helix bundles have previously been designed to catalyse the hydrolysis of activated esters. The catalysts exhibit rate enhancements of more than three orders of magnitude, chiral discrimination and saturation kinetics [1,2]. The suggested mechanism includes cooperative nucleophilic and general acid catalysis by HisH+-His pairs.We have now expanded the concept of His catalysis to new reactive site structures and determined conditions under which the generalacid catalysis becomes important.