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

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• 作者：Ilaria Pettinati¹ ; Jü ; rgen Brem¹ ; Sook Y. Lee² ; Peter J. McHugh² ; Christopher J. Schofield¹ ; ^{christopher.schofield@chem.ox.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：β-lactam antibiotic and cancer drug resistance ; metallo β-lactamase fold protein ; DNA repair ; RNA processing ; hydrogen sulphide metabolism ; nuclease
• 刊名：Trends in Biochemical Sciences
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：41
• 期：4
• 页码：338-355
• 全文大小：3473 K

文摘

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.