Regulation of the activity of lactate dehydrogenases from four lactic acid bacteria

Despite high similarity in sequence and catalytic properties, the L-lactate dehydrogenases (LDH) in lactic acid bacteria (LAB) display differences in their regulation which may arise from their adaptation to different habitats. We combined experimental and computational approaches to investigate the effects of fructose-1,6-bisphosphate (FBP), phosphate (Pi) and ionic strength (NaCl concentration) on 6 LDHs from 4 LABs studied at pH 6 and pH 7. We find: (1) The extent of activation by FBP (Kact) differs: L. plantarum LDH is not regulated by FBP; the other LDHs are activated with increasing sensitivity in the following order: E. faecalis LDH2 ≤ L. lactis LDH2 < E. faecalis LDH1 < L. lactis LDH1 ≤ S. pyogenes LDH. This trend reflects the electrostatic properties in the allosteric binding site of the LDH enzymes. (2) For L. plantarum, S. pyogenes and E. faecalis, the effects of Pi are distinguishable from the effect of changing ionic strength by adding NaCl. (3) Addition of Pi inhibits E. faecalis LDH2 whereas, in the absence of FBP, Pi is an activator of S. pyogenes LDH, E. faecalis LDH1, and L. lactis LDH1 and LDH2 at pH 6. These effects can be interpreted by considering the computed binding affinities of Pi to the catalytic and allosteric binding sites of the enzymes modeled in protonation states corresponding to pH 6 and pH 7. Overall, the results show a subtle interplay between the effects of Pi, FBP and pH, which results in different regulatory effects on the LDHs of different LABs.

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Created: 19th Feb 2014 at 13:08

Last updated: 8th Nov 2017 at 14:21

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