Bacillus subtilis FolE is sustained by the ZagA zinc metallochaperone and the alarmone ZTP under conditions of zinc deficiency.
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YciC has been renamed ZagA (ZTP-activated GTPase A)
"Bacillus subtilis YciC zinc metallochaperone (here renamed ZagA for ZTP activated GTPase A)"
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ZagA represents first demonstrated physical interaction between COG0523 metallochaperone and client protein
"Here, we demonstrate that the Bacillus subtilis YciC zinc metallochaperone (here renamed ZagA for ZTP activated GTPase A) supports de novo folate biosynthesis under conditions of zinc limitation, and interacts directly with the zinc-dependent GTP cyclohydrolase IA, FolE (GCYH-IA)"
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ZTP alarmone activates ZagA interaction with FolE
"ZTP, a signal of 10-formyl-tetrahydrofolate (10f-THF) deficiency in bacteria, transiently accumulates as FolE begins to fail, stimulates the interaction between ZagA and FolE, and thereby helps to sustain folate synthesis despite declining zinc availability."
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Sophisticated feedback circuit maintains folate biosynthesis during zinc limitation
"At the onset of zinc limitation, the purine biosynthetic intermediate 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), also known as ZMP, accumulates and is known to be phosphorylated to ZTP. The Zur-regulated metallochaperone ZagA is activated by ZTP to bind FolE, and this interaction likely allows delivery of zinc to FolE to sustain folate synthesis."
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ZagA directly transfers zinc to FolE for tetrahydrofolate biosynthesis
"this interaction likely allows delivery of zinc to FolE to sustain folate synthesis"
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ZTP is produced from ZMP during zinc limitation and folate deficiency
"At the onset of zinc limitation, the purine biosynthetic intermediate 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), also known as ZMP, accumulates and is known to be phosphorylated to ZTP"