期刊
FEBS LETTERS
卷 591, 期 3, 页码 468-478出版社
WILEY
DOI: 10.1002/1873-3468.12554
关键词
antibiotic; biosynthesis; nonheme iron; nucleoside; oxygenase; translocase I
资金
- National Institutes of Health [AI087849]
- National Center for Advancing Translational Sciences Grant [UL1TR000117]
LipL and Cpr19 are nonheme, mononuclear Fe(II)-dependent, alpha-ketoglutarate (alpha KG): UMP oxygenases that catalyze the formation of CO2, succinate, phosphate, and uridine-5'-aldehyde, the last of which is a biosynthetic precursor for several nucleoside antibiotics that inhibit bacterial translocase I (MraY). To better understand the chemistry underlying this unusual oxidative dephosphorylation and establish a mechanistic framework for LipL and Cpr19, we report herein the synthesis of two biochemical probes-[1',3',4',5',5'-H-2] UMP and the phosphonate derivative of UMP-and their activity with both enzymes. The results are consistent with a reaction coordinate that proceeds through the loss of one H-2 atom of [1',3',4',5',5'-H-2] UMP and stereospecific hydroxylation geminal to the phosphoester to form a cryptic intermediate, (5'R)-5'-hydroxy-UMP. Thus, these enzyme catalysts can additionally be assigned as UMP hydroxylase-phospholyases.
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