The Chemical Biology of Human Metallo-β-Lactamase Fold Proteins.

Ilaria Pettinati, Jürgen Brem, Sook Y Lee, Peter J McHugh, Christopher J Schofield

Journal: Trends in biochemical sciences 2017;41(4):338-355

PMID: 26805042

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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.

Address: Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.; Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.; Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. Electronic address: [email protected].

DOI: 10.1016/j.tibs.2015.12.007

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https://assays.cancer.gov/non-CPTAC-2684

MeSH Terms: Arabidopsis, Bacteria, DNA Repair Enzymes, Exodeoxyribonucleases, Gene Expression, Humans, Hydrolysis, Mitochondrial Proteins, Muscle Proteins, Nuclear Proteins, Nucleocytoplasmic Transport Proteins, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Folding, Protein Interaction Domains and Motifs, Thiolester Hydrolases, Zinc, beta-Lactamases, beta-Lactams