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.
The C-P lyase complex in bacteria catalyzes the transformation of class="Chemical">phosphonates to class="Chemical">pan class="Chemical">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.
Authors: María B Cassera; Meng-Chiao Ho; Emilio F Merino; Emmanuel S Burgos; Agnes Rinaldo-Matthis; Steven C Almo; Vern L Schramm Journal: Biochemistry Date: 2011-02-15 Impact factor: 3.162
Authors: Siddhesh S Kamat; Ashima Bagaria; Desigan Kumaran; Gregory P Holmes-Hampton; Hao Fan; Andrej Sali; J Michael Sauder; Stephen K Burley; Paul A Lindahl; Subramanyam Swaminathan; Frank M Raushel Journal: Biochemistry Date: 2011-02-04 Impact factor: 3.162