Glutamate gamma-semialdehyde as a natural transition state analogue inhibitor of Escherichia coli glucosamine-6-phosphate synthase.
Pyrroline-5-carboxylate, an intermediate in the biosynthesis and degradation of glutamate, proline, and ornithine, acts as a strong reversible inhibitor of glucosamine-6-phosphate synthase, competitive with respect to glutamine. Proton magnetic resonance spectroscopy shows that, under these conditions, pyrroline-5-carboxylate exists in rapid equilibrium with glutamate gamma-semialdehyde (0.05%). The observed variation of Ki with pH is consistent with inhibition by this rare species. Glutamate gamma-semialdehyde is expected to react reversibly with a cysteine residue at the active site, identified by earlier inactivation studies, to form an analogue of a tetrahedral intermediate in glutamine hydrolysis. The apparent Ki value of glutamate gamma-semialdehyde is approximately 3 x 10(-8) M.
Bearne
S L
SL
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599-7260, USA.
Wolfenden
R
R
D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D005971:Glutamates / Q000494:pharmacology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D005971:Glutamates; D011758:Pyrroles; C015485:delta-1-pyrroline-5-carboxylate; C021199:glutamic acid gamma-semialdehyde; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)