LarC Cyclometallase

(2020) Encyclopedia of Inorganic and Bioinorganic Chemistry — ISBN: [9781119951438], published

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Abstract
Bacterial lactate racemase is a nickel‐dependent enzyme that contains the nickel‐pincer nucleotide (NPN) cofactor. The LarC enzyme participates in NPN biosynthesis by inserting nickel ion into the cofactor precursor, forming the mature NPN. This reaction, known in organometallic chemistry as a cyclometalation, is characterized by the formation of new NiC and NiS σ bonds. LarC is therefore the first cyclometallase identified in nature. LarC behaves as a single turnover enzyme in vitro and its reaction requires Mn2+‐dependent CTP hydrolysis. The crystal structure of the C‐terminal domain of LarC (LarC2) revealed the CTP binding pocket. LarC1 domain, on the other hand, is responsible for the cyclometalation reaction. Its structure has not been solved but a model has been constructed using evolutionary information. LarC1 catalysis requires acidic residues, which are probably involved in proton abstraction from the NPN precursor and nickel transfer, but the mechanism remains elusive.
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Desguin, B. (2020). LarC Cyclometallase. In Robert A Scott, John Wiley & Sons (ed.), Encyclopedia of Inorganic and Bioinorganic Chemistry. https://doi.org/10.1002/9781119951438.eibc2737