title: The Chemical Biology of Human Metallo-β-Lactamase Fold Proteins.
abstract: The αββα metallo β-lactamase (MBL) fold (MBLf) was first observed in bacterial enzymes that catalyze the hydrolysis of almost all β-lactam antibiotics, but is now known to be widely distributed. The MBL core protein fold is present in human enzymes with diverse biological roles, including cell detoxification pathways and enabling resistance to clinically important anticancer medicines. Human (h)MBLf enzymes can bind metals, including zinc and iron ions, and catalyze a range of chemically interesting reactions, including both redox (e.g., ETHE1) and hydrolytic processes (e.g., Glyoxalase II, SNM1 nucleases, and CPSF73). With a view to promoting basic research on MBLf enzymes and their medicinal targeting, here we summarize current knowledge of the mechanisms and roles of these important molecules.
authors.affiliation: Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pettinati
authors.affiliation: Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brem
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
authors.forename: Sook Y
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McHugh
authors.affiliation: Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. Electronic address: christopher.schofield@chem.ox.ac.uk.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D045643:DNA Repair Enzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases; D015870:Gene Expression; D006801:Humans; D006868:Hydrolysis; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D013869:Thiolester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D047090:beta-Lactams / Q000737:chemistry / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D045643:DNA Repair Enzymes; D005090:Exodeoxyribonucleases; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D013869:Thiolester Hydrolases; D015032:Zinc; D001618:beta-Lactamases; D047090:beta-Lactams; D000099301:Hydroxyacylglutathione Hydrolase; C483228:ETHE1 protein, human; C495444:PNKD protein, human; C493741:DCLRE1B protein, human
keywords: DNA repair; RNA processing; hydrogen sulphide metabolism; metallo β-lactamase fold protein; nuclease; β-lactam antibiotic and cancer drug resistance