83983-81-7Relevant academic research and scientific papers
DXP synthase-catalyzed c-n bond formation: Nitroso substrate specificity studies guide selective inhibitor design
Morris, Francine,Vierling, Ryan,Boucher, Lauren,Bosch, Juergen,Freel Meyers, Caren L.
, p. 1309 - 1315 (2013)
1-Deoxy-D-xylulose 5-phosphate (DXP) synthase catalyzes the first step in the nonmammalian isoprenoid biosynthetic pathway to form DXP from pyruvate and D-glyceraldehyde 3-phosphate (D-GAP) in a thiamin diphosphate-dependent manner. Its unique structure and mechanism distinguish DXP synthase from its homologues and suggest that it should be pursued as an anti-infective drug target. However, few reports describe any development of selective inhibitors of this enzyme. Here, we reveal that DXP synthase catalyzes C-N bond formation and exploit aromatic nitroso substrates as active site probes. Substrate specificity studies reveal a high affinity of DXP synthase for aromatic nitroso substrates compared to the related ThDP-dependent enzyme pyruvate dehydrogenase (PDH). Results from inhibition and mutagenesis studies indicate that nitroso substrates bind to E. coli DXP synthase in a manner distinct from that of D-GAP. Our results suggest that the incorporation of aryl acceptor substrate mimics into unnatural bisubstrate analogues will impart selectivity to DXP synthase inhibitors. As a proof of concept, we show selective inhibition of DXP synthase by benzylacetylphosphonate (BnAP).
Transketolase Catalyzed Synthesis of N-Aryl Hydroxamic Acids
Fúster Fernández, Inés,Hecquet, Laurence,Fessner, Wolf-Dieter
supporting information, p. 612 - 621 (2021/12/08)
Hydroxamic acids are metal-chelating compounds that show important biological activity including anti-tumor effects. We have recently engineered the transketolase from Geobacillus stearothermopilus (TKgst) to convert benzaldehyde as a non-natur
