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Evidence that oxidative dephosphorylation by the nonheme Fe( II ), α‐ketoglutarate: UMP oxygenase occurs by stereospecific hydroxylation
Author(s) -
Goswami Anwesha,
Liu Xiaodong,
Cai Wenlong,
Wyche Thomas P.,
Bugni Tim S.,
Meurillon Maïa,
Peyrottes Suzanne,
Perigaud Christian,
aka Koichi,
Rohr Jürgen,
Van Lanen Steven G.
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12554
Subject(s) - chemistry , hydroxylation , dephosphorylation , stereochemistry , oxidative phosphorylation , enzyme , stereospecificity , biochemistry , uridine , oxygenase , catalysis , phosphatase , rna , gene
LipL and Cpr19 are nonheme, mononuclear Fe( II )‐dependent, α‐ketoglutarate (α KG ): UMP oxygenases that catalyze the formation of CO 2 , 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′‐ 2 H] 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 2 H atom of [1′,3′,4′,5′,5′‐ 2 H] 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.