Evidence that oxidative dephosphorylation by the nonheme Fe(II), α-ketoglutarate:UMP oxygenase occurs by stereospecific hydroxylation.

Abstract:

:LipL and Cpr19 are nonheme, mononuclear Fe(II)-dependent, α-ketoglutarate (αKG):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'-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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Goswami A,Liu X,Cai W,Wyche TP,Bugni TS,Meurillon M,Peyrottes S,Perigaud C,Nonaka K,Rohr J,Van Lanen SG

doi

10.1002/1873-3468.12554

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

468-478

issue

3

eissn

0014-5793

issn

1873-3468

journal_volume

591

pub_type

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