title: Catalytic mechanisms of metallohydrolases containing two metal ions.
abstract: At least one-third of enzymes contain metal ions as cofactors necessary for a diverse range of catalytic activities. In the case of polymetallic enzymes (i.e., two or more metal ions involved in catalysis), the presence of two (or more) closely spaced metal ions gives an additional advantage in terms of (i) charge delocalisation, (ii) smaller activation barriers, (iii) the ability to bind larger substrates, (iv) enhanced electrostatic activation of substrates, and (v) decreased transition-state energies. Among this group of proteins, enzymes that catalyze the hydrolysis of ester and amide bonds form a very prominent family, the metallohydrolases. These enzymes are involved in a multitude of biological functions, and an increasing number of them gain attention for translational research in medicine and biotechnology. Their functional versatility and catalytic proficiency are largely due to the presence of metal ions in their active sites. In this chapter, we thus discuss and compare the reaction mechanisms of several closely related enzymes with a view to highlighting the functional diversity bestowed upon them by their metal ion cofactors.
authors.affiliation: Department of Chemistry, National University of Ireland, Maynooth, Maynooth, Co. Kildare, Ireland. Electronic address: natasa.mitic@nuim.ie.
authors.forename: Nataša
authors.initials: N
authors.lastname: Mitić
authors.affiliation: Department of Chemistry, National University of Ireland, Maynooth, Maynooth, Co. Kildare, Ireland; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Miraula
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Selleck
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Kieran S
authors.initials: KS
authors.lastname: Hadler
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Concepción, Concepción, Chile.
authors.forename: Elena
authors.initials: E
authors.lastname: Uribe
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Pedroso
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: schenk@uq.edu.au.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schenk
mesh_terms: D000626:Aminopeptidases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D055162:Biocatalysis; D002413:Cations, Divalent; D006801:Humans; D006868:Hydrolysis; D019216:Metals, Heavy / Q000737:chemistry*; D008958:Models, Molecular; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry*; D055672:Static Electricity; D013379:Substrate Specificity; D013816:Thermodynamics; D014512:Ureohydrolases / Q000737:chemistry*; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D002413:Cations, Divalent; D019216:Metals, Heavy; D010727:Phosphoric Diester Hydrolases; C038133:glycerophosphodiester phosphodiesterase; D000626:Aminopeptidases; C511921:METAP1D protein, human; D001618:beta-Lactamases; C496277:metallo-beta-lactamase L1, Stenotrophomonas maltophilia; D014512:Ureohydrolases; C019625:agmatinase
keywords: Agmatinases; Aminopeptidases; Binuclear metalloenzymes; Catalytic mechanisms; Metallo-β-lactamases; Organophosphate-degrading enzymes; Purple acid phosphatases