OMP decarboxylase: an experimental test of electrostatic destabilization of the enzyme-substrate complex.
6-Methylaminouridine 5'-phosphate (MAUMP) inhibits OMP decarboxylase (Ki = 3 x 10-6 M) maximally at pH values where its amino group is uncharged. Comparison of the chemical shift of free [7-13C]-MAUMP in solutions of varying pH, with that of the enzyme-bound species confirms that this inhibitor is bound with its amino group uncharged. This enzyme's apparent lack of affinity for a cationic substituent, located near the position that would ordinarily be occupied by the scissile carboxylate group of the substrate, does not appear to support the view that the E-S complex is destabilized by electrostatic repulsion in the ground state.
Callahan
Brian P
BP
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27514-7260, USA.
Wolfenden
Richard
R
D004795:Enzyme Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
C494483:6-methylaminouridine 5'-phosphate; D008024:Ligands; C005417:orotidylic acid; D014542:Uridine Monophosphate; D009964:Orotidine-5'-Phosphate Decarboxylase