Slow-binding inhibition of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase.
2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase is a key enzyme in the Entner-Doudoroff pathway of bacteria. It catalyzes the reversible production of KDPG from pyruvate and D-glyceraldehyde 3-phosphate through a class I Schiff base mechanism. On the basis of aldolase mechanistic pathway, various pyruvate analogues bearing beta-diketo structures were designed and synthesized as potential inhibitors. Their capacity to inhibit aldolase catalyzed reaction by forming stabilized iminium ion or conjugated enamine were investigated by enzymatic kinetics and UV-vis difference spectroscopy. Depending of the substituent R (methyl or aromatic ring), a competitive or a slow-binding inhibition takes place. These results were examined on the basis of the three-dimensional structure of the enzyme.
Braga
Rémi
R
Université Paul Sabatier, LSPCMIB, UMR 5068, Groupe de Chimie Organique Biologique, Bât IIR1, 118 Route de Narbonne, 31062 Toulouse Cedex 4, France.
Hecquet
Laurence
L
Blonski
Casimir
C
D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D011773:Pyruvates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013057:Spectrum Analysis / Q000379:methods; D013997:Time Factors
D011773:Pyruvates; C007691:acetylpyruvic acid; D000446:Aldehyde-Lyases; C100131:phospho-2-keto-3-deoxy-gluconate aldolase