tRNA-modifying protein YgfZ (YgfZ)

tRNA-modifying protein YgfZ is a conserved folate-binding protein that plays a pivotal role in the biogenesis and repair of iron-sulfur (Fe-S) clusters in bacteria and eukaryotes [1, 3]. In Escherichia coli, it is specifically required for the maturation of [4Fe-4S] clusters in radical S-adenosylmethionine (SAM) enzymes, such as MiaB and RimO, which catalyze essential modifications of tRNA and ribosomal proteins [8, 26]. YgfZ also functions as a regulator of chromosomal replication initiation by modulating the levels of ATP-DnaA and participates in the cellular response to oxidative stress [9, 18]. The human ortholog, IBA57, is a critical mitochondrial assembly factor, and its deficiency leads to severe neurodegenerative and metabolic conditions, including Multiple Mitochondrial Dysfunctions Syndrome 3 (MMDS3) [20, 23]. While YgfZ is considered a potential target for the development of new antimicrobial agents due to its role in bacterial fitness and stress resistance, its structural similarity to the human mitochondrial counterpart poses a significant challenge for achieving therapeutic selectivity [14, 27]. Current research focuses on understanding its precise mechanism of action and its interaction with other components of the Fe-S cluster assembly machinery [5, 30].

Other names

yzzWb2898JW2866COG0354 family proteinFolate-binding protein YgfZ

YgfZ facilitates the assembly and repair of [4Fe-4S] clusters by acting as a folate-dependent factor that likely removes deleterious one-carbon units or stabilizes cluster transfer to target enzymes like MiaB and RimO [1, 2, 5]. It interacts with the IscA/SufA scaffold proteins to promote the maturation of specific Fe-S proteins [7, 8].