The Catalytic Mechanisms of Binuclear Metallohydrolases

Binuclear metallohydrolases are a structurally diverse of enzymes that use binuclear metal ion centers to the hydrolysis of amides and esters of carboxylic phosphoric acids. Representatives are listed in Table 1, with their metal ion composition and, if known, their role (s). Several of these enzymes are either targets drug design against a wide variety of human disorders, osteoporosis, cancer, cystic fibrosis, and depression, are of significance in bioremediation since they can be to degrade pesticides or organophosphorus nerve. 1996, Wilcox summarized the then current knowledge the structure, function, and mechanism of all known metallohydrolases. 1 In subsequent years more articles followed, 2 focusing on the binuclear -containing arginases, catalases, and enolases, 3 the /Thr protein phosphatases (in particular calcineurin), 4-6 Despite their structural versatility and variations in metal ion (Table 1), binuclear metallohydrolases employ of a similar basic mechanism. Similarities in the coordination sphere are found across the entire family enzymes (Figure 1), but in the proposed models for, the identity of the attacking nucleophile, the of reaction intermediates, and the relative of the metal ions vary substantially. , an updated review of the current understanding of -catalyzed reactions is presented. The motivation to present, compare, and critically assess current for metal ion assisted hydrolytic reaction mechanisms. focus here is on four systems, purple acid (PAPs), Ser/Thr protein phosphatases (PPs), 3¢-5¢ exonucleases, and 5¢-nucleotidases (5¢-NTs), which have to major advancement of our current understanding the catalytic mechanisms that operate in such enzymes. three of the four enzymes (PAPs, PPs, and 5¢-NTs) evolutionarily related, 11 the enzymes selected for this are diverse with respect to their structure, metal ion, and function. The authors have concentrated on references covering the past decade; however, earlier literature is included where appropriate. We our apologies to researchers whose contributions may have been covered by this review. terms of the catalytic mechanism, the identity of the -initiating nucleophile and the roles of the metal ions catalysis are addressed. Where possible, predicted structures transition states and their stabilization are discussed. description of an enzyme family concludes with an of the currently accepted model for its catalytic. The various models proposed for the hydrolytic mechanism are compared in context with observed in physicochemical and functional properties. to Wilcox’s review, this article reflects the recent of bioinorganic chemists. However, since many metallohydrolases are targets for the development drugs, pesticides and anti-warfare agents, structural and those involved in drug discovery and development find this review useful and timely.