Ancient complexes of iron and sulfur modulate oncogenes and oncometabolism
Current Opinion in Chemical Biology 76, 102338
Inorganic complexes of iron and sulfur, that is, iron-sulfur [FeS] clusters, have played a fundamental role in life on Earth since the prebiotic period. These clusters were involved in elementary reactions leading to the emergence of life and, since then, gained function in processes, such as respiration, replication, transcription, and the immune response. We discuss how three [FeS] proteins involved in the innate immune response play a role in oncogene expression/function and oncometabolism. Our analysis highlights the importance of future research into understanding the [FeS] clusters' roles in cancer progression and proliferation. The outcomes of these studies will help identify new targets and develop new anticancer therapeutics.
VITAS, a sensitive in vivo selection assay to discover enzymes producing antiviral natural products
Chemical Communications 59, 5419-5422
To discover new broad-spectrum antiviral nucleotide analogues from natural resources or through protein engineering, we have developed a sensitive in vivo selection assay named Viral polymerase-Inhibition Toxin-Associated Selection (VITAS). We show that the assay works with enzymes from three Kingdoms of life.
Radical-SAM dependent nucleotide dehydratase (SAND), rectification of the names of an ancient iron-sulfur enzyme using NC-IUBMB recommendations
Front. Mol. Biosci. 9:1032220
In 1789, the influential French chemist Antoine-Laurent Lavoisier described his view of science and its langague in his book Traité élémentaire de chimie. According to the Robert Kerr’s translation it states (Lavoisier, 1790): “As ideas are preserved and communicated by means of words, it necessarily follows that we cannot improve the language of any science without at the same time improving the science itself; neither can we, on the other hand, improve a science without improving the language or nomenclature which belongs to it.” This view reminds us of Confucius’s earlier doctrine, the rectification of names (Steinkraus, 1980; Lau, 2000). Confucius believed that rectification of names is imperative. He explained (Steinkraus, 1980; Lau, 2000): “If language is incorrect, then what is said does not concord with what was meant, what is to be done cannot be affected. If what is to be done cannot be affected, then rites and music will not flourish. If rites and music do not flourish, then mutilations and lesser punishments will go astray. And if mutilations and lesser punishments go astray, then the people have nowhere to put hand or foot. Therefore the gentleman uses only such language as is proper for speech, and only speaks of what it would be proper to carry into effect. The gentleman in what he says leaves nothing to mere chance.” Inspired by these views, we make the analogy that the progress of science and the language used to describe it are two entangled electrons. This entanglement highlights the importance of introducing systemic names for enzymes using EC classification and the ever-growing problem of protein names (McDonald and Tipton, 2021). Here, we tackle one specific case of iron-sulfur ([FeS]) enzymes. We show that the language used to describe a conserved [FeS] enzyme of the innate immune system, i.e., viperin or RSAD2, is now inadequate and disentangled from its science. We discuss that the enzyme has cellular functions beyond its antiviral activity and that eukaryotic and prokaryotic enzymes catalyse the same chemical reactions. To prevent bias towards antiviral activity while studying various biochemical activities of the enzyme and using scientifically incorrect terms like “prokaryotic viperins,” we rectify the language describing the enzyme. Based on NC-IUBMB recommendations, we introduce the nomenclature S-adenosylmethionine (SAM) dependent Nucleotide Dehydratase (SAND).