Inhibition of mandelate racemase by the substrate-intermediate-product analogue 1,1-diphenyl-1-hydroxymethylphosphonate

Rodney K M Burley; Stephen L Bearne

doi:10.1016/j.bmcl.2005.06.060

Inhibition of mandelate racemase by the substrate-intermediate-product analogue 1,1-diphenyl-1-hydroxymethylphosphonate

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4342-4. doi: 10.1016/j.bmcl.2005.06.060.

Authors

Rodney K M Burley¹, Stephen L Bearne

Affiliation

¹ Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 1X5.

PMID: 16039120
DOI: 10.1016/j.bmcl.2005.06.060

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacterial Proteins / antagonists & inhibitors
Binding Sites
Binding, Competitive
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Ligands
Molecular Structure
Organophosphorus Compounds / chemical synthesis
Organophosphorus Compounds / chemistry*
Organophosphorus Compounds / pharmacology
Pseudomonas putida / enzymology*
Racemases and Epimerases / antagonists & inhibitors*
Structure-Activity Relationship

Substances

1,1-diphenyl-1-hydroxymethylphosphonate
Bacterial Proteins
Enzyme Inhibitors
Ligands
Organophosphorus Compounds
Racemases and Epimerases
mandelate racemase