Inhibition of mandelate racemase by the substrate-intermediate-product analogue 1,1-diphenyl-1-hydroxymethylphosphonate.
Mandelate racemase has been studied as a paradigm for enzyme-catalyzed abstraction of a proton from carbon acids with relatively high pKa values. 1,1-Diphenyl-1-hydroxymethylphosphonate is a substrate-intermediate-product analogue and is a modest competitive inhibitor of the enzyme (Ki=1.41+/-0.09 mM), suggesting that simultaneous binding of the two phenyl groups obviates mimicry of the aci-carboxylate function of the intermediate by the phosphonate group.
Burley
Rodney K M
RK
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 1X5.
Bearne
Stephen L
SL
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D001665:Binding Sites; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016958:Pseudomonas putida / Q000201:enzymology*; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C506220:1,1-diphenyl-1-hydroxymethylphosphonate; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008024:Ligands; D009943:Organophosphorus Compounds; D019998:Racemases and Epimerases; C021540:mandelate racemase