Inhibition of mandelate racemase by alpha-fluorobenzylphosphonates.
Mandelate racemase catalyzes the interconversion of the enantiomers of mandelic acid. The enzyme binds the intermediate analogues (R)- and (S)-alpha-fluorobenzylphosphonate, and alpha,alpha-difluorobenzylphosphonate with 100-2500 times less affinity than it exhibits for (R,S)-alpha-hydroxybenzylphosphonate at pH 7.5. This apparent low affinity, relative to that of alpha-hydroxybenzylphosphonate, arises from the altered pKa values of the alpha-fluorobenzylphosphonates. For example, (S)-alpha-fluorobenzylphosphonate is bound with the same affinity as the substrate at pH 7.5, but this affinity is increased approximately 6-fold at pH 6.3.
St Maurice
Martin
M
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5.
Bearne
Stephen L
SL
Lu
Wallach
W
Taylor
Scott D
SD
D001593:Benzyl Compounds / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry; D008333:Mandelic Acids / Q000378:metabolism; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D016958:Pseudomonas putida / Q000201:enzymology; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D001593:Benzyl Compounds; D004791:Enzyme Inhibitors; D006845:Hydrocarbons, Fluorinated; D008333:Mandelic Acids; D063065:Organophosphonates; D011994:Recombinant Proteins; D019998:Racemases and Epimerases; C021540:mandelate racemase; D008274:Magnesium; C037938:mandelic acid