Potent inhibition of the C-P lyase nucleosidase PhnI by Immucillin-A triphosphate.

ABSTRACT

The C-P lyase complex in bacteria catalyzes the transformation of phosphonates to orthophosphate under conditions of phosphate starvation. The first committed step in the C-P lyase-catalyzed reaction is the displacement of adenine from MgATP by phosphonate substrates, yielding ribose-1-phosphonate-5-triphosphate. In the C-P lyase complex, this reaction is catalyzed by the nucleosidase PhnI and modulated by the addition of PhnG, PhnH, and PhnL. Here we describe the synthesis of Immucillin-A triphosphate, a mimic of the transition state structure for the nucleosidase reaction catalyzed by PhnI. This compound inhibits PhnI with a dissociation constant of 20 nM at pH 7.5.