title: Metallophosphoesterases: structural fidelity with functional promiscuity.
abstract: Calcineurin-like metallophosphoesterases (MPEs) form a large superfamily of binuclear metal-ion-centre-containing enzymes that hydrolyse phosphomono-, phosphodi- or phosphotri-esters in a metal-dependent manner. The MPE domain is found in Mre11/SbcD DNA-repair enzymes, mammalian phosphoprotein phosphatases, acid sphingomyelinases, purple acid phosphatases, nucleotidases and bacterial cyclic nucleotide phosphodiesterases. Despite this functional diversity, MPEs show a remarkably similar structural fold and active-site architecture. In the present review, we summarize the available structural, biochemical and functional information on these proteins. We also describe how diversification and specialization of the core MPE fold in various MPEs is achieved by amino acid substitution in their active sites, metal ions and regulatory effects of accessory domains. Finally, we discuss emerging roles of these proteins as non-catalytic protein-interaction scaffolds. Thus we view the MPE superfamily as a set of proteins with a highly conserved structural core that allows embellishment to result in dramatic and niche-specific diversification of function.
authors.affiliation: *Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Nishad
authors.initials: N
authors.lastname: Matange
authors.affiliation: †Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
authors.forename: Marjetka
authors.initials: M
authors.lastname: Podobnik
authors.affiliation: *Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Sandhya S
authors.initials: SS
authors.lastname: Visweswariah
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology; D005092:Exonucleases / Q000737:chemistry / Q000502:physiology; D006801:Humans; D000076228:MRE11 Homologue Protein; D008667:Metalloproteins / Q000737:chemistry / Q000502:physiology; D017510:Protein Folding; D013329:Structure-Activity Relationship
chemical_list: D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D008667:Metalloproteins; D005092:Exonucleases; D000076228:MRE11 Homologue Protein