Mn²⁺‐DependentL‐Ascorbate 6‐Phosphate Lactonase

Abstract

This enzyme (UlaG) catalyzes the first catabolic reaction in the ascorbate assimilation pathway, the divalent‐metal‐dependent hydrolytic lactone ring opening of L ‐ascorbate 6‐phosphate into 3‐keto‐ L ‐gulonate 6‐phosphate. Apart from its physiologic reaction, UlaG can also cleave phosphodiester bond linkages within substrates such as cyclic nucleoside monophosphates and phosphatase‐type substrates [e.g., bis(p‐nitrophenylphosphate), bis‐pNPP]. The crystal structures of the UlaG apoenzyme and the Mn 2+ holoenzyme have revealed a novel structural paradigm for an entire new family of MBL like metalloenzymes, characterized by an RNase Z‐reminiscent fold, an intricate hexameric arrangement, and a mononuclear or dinuclear metal site. This hexameric enzyme is absolutely dependent on Mn 2+ or Co 2+ for activity and becomes severely inhibited by Zn 2+ . Phylogenetic analyses show that present‐day UlaG may have originated by gene duplication from an ancestral RNA‐metabolizing template and evolved through extensive neofunctionalization to acquire sugar‐phosphate hydrolytic activity.