Introduction Metals in Biology: {alpha}-Ketoglutarate/Iron Dependent Dioxygenases [Metabolism]

July 7th, 2015 by Guengerich, F. P.

Four Minireviews deal with aspects of the α-ketoglutarate/iron dependent dioxygenases in this eighth Thematic Series on Metals in Biology. The Minireviews cover a general introduction and synopsis of the current understanding of mechanisms of catalysis, the roles of these dioxygenases in post-translational protein modification and de-modification, the roles of the ten-eleven translocation (Tet) dioxygenases in the modification of methylated bases (5mC, T) in DNA relevant to epigenetic mechanisms, and the roles of the AlkB-related dioxygenases in the repair of damaged DNA and RNA. The use of α-ketoglutarate (alternatively termed 2-oxoglutarate) as a co-substrate in so many oxidation reactions throughout much of nature is notable and has surprisingly emerged from biochemical and genomic analysis. About 60 of these enzymes are now recognized in humans, and a number have been identified as having critical functions.

Introduction: Metals in Biology – Metals at the Host-Pathogen Interface [Molecular Bases of Disease]

June 8th, 2015 by Guengerich, F. P.

This seventh Metals in Biology Thematic Series deals with the metal-based interactions of mammalian hosts with pathogens. Both pathogens and host have complex regulatory systems for metal homeostasis. Understanding these provides strategies for fighting pathogens, either by excluding essential metals from the microbes, by delivery of excess metals to cause toxicity, or by complexing metals in microorganisms. Intervention is possible by delivery of complexing reagents or by targeting the microbial regulatory apparatus.

Thematic Minireview Series: Metals in Biology 2014 [Microbiology]

August 26th, 2014 by Guengerich, F. P.

This thematic series, the sixth in the Metals in Biology collection beginning in 2009, addresses the issue of why certain metals are used by particular enzymes, as well as the consequences of using the wrong metal. This prologue introduces the 2014 Metals in Biology. The first Minireview in the series deals with general aspects of metal specificity, and the next two deal with specific cases, the enzyme ribonucleotide reductase and iron/manganese homeostasis in the bacterium Bacillus subtilis. The fourth discusses metal selection in oxidative stress, and the final Minireview discusses lysosome-related organelles as mediators of metal homeostasis.