Functional analysis of the Mn2+ requirement in the catalysis of ureohydrolases arginase and agmatinase - a historical perspective

Abstract

Ureohydrolases form a conserved family of enzymes with a strict requirement for divalent metal ions for catalytic activity. They catalyze the hydrolysis of the guanidino group and produce urea. In their active sites six highly conserved amino acid residues form a binding pocket for two catalytically essential metal ions that are needed to activate a water molecule to initiate the hydrolysis of the guanidino group in a nucleophilic attack. Focus in this review is on two members of the ureohydrolase family, the Mn²⁺-dependent arginase and agmatinase, which play important roles in functions related to replication and cell survival. We will focus in particular on Mn²⁺ binding interactions, and on how this metal ion contributes to the reaction catalyzed by these enzymes. We also include the agmatinase-like protein (ALP) because it is functionally closely related to agmatinase, also requires at least one Mn²⁺ ion for catalytic activity, but may possess an active site that differs significantly from all other known ureohydrolases.