7uld
GTP complex of F420-gamma glutamyl ligase (CofE) from Archaeoglobus fulgidus
Structural highlights
FunctionCOFE_ARCFU Catalyzes the GTP-dependent successive addition of two L-glutamates to the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) to form coenzyme F420-0-glutamyl-glutamate (F420-2), with a gamma-linkage between the two glutamates. May be able to add up to four gamma-linked glutamates, since F420-4 is a species that was isolated from A.fulgidus.[1] Publication Abstract from PubMedPoly-gamma-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates and F(420). Despite decades of research, key mechanistic questions remain as to how enzymes successively add glutamates to poly-gamma-glutamate chains while maintaining cofactor specificity. Here, we show how poly-gamma-glutamylation of folate and F(420) by folylpolyglutamate synthases and gamma-glutamyl ligases, non-homologous enzymes, occurs via processive addition of L-glutamate onto growing gamma-glutamyl chain termini. We further reveal structural snapshots of the archaeal gamma-glutamyl ligase (CofE) in action, crucially including a bulged-chain product that shows how the cofactor is retained while successive glutamates are added to the chain terminus. This bulging substrate model of processive poly-gamma-glutamylation by terminal extension is arguably ubiquitous in such biopolymerisation reactions, including addition to folates, and demonstrates convergent evolution in diverse species from archaea to humans. Poly-gamma-glutamylation of biomolecules.,Bashiri G, Bulloch EMM, Bramley WR, Davidson M, Stuteley SM, Young PG, Harris PWR, Naqvi MSH, Middleditch MJ, Schmitz M, Chang WC, Baker EN, Squire CJ Nat Commun. 2024 Feb 12;15(1):1310. doi: 10.1038/s41467-024-45632-1. PMID:38346985[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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