Dihydrodipicolinate synthase is not inhibited by its substrate, (S)-aspartate beta-semialdehyde.
DHDPS (dihydrodipicolinate synthase; EC 4.2.1.52) is the enzyme that catalyses the first unique step of lysine biosynthesis in plants and micro-organisms. As such, it has attracted much attention as a target for herbicide and anti-microbial action. DHDPS has two substrates: pyruvate and ( S )-aspartate beta-semialdehyde [( S )-ASA]. There are various literature reports that suggest that high levels of ( S )-ASA inhibit the enzyme [Karsten (1997) Biochemistry 36, 1730-1739; Stahly (1969) Biochim. Biophys. Acta 191, 439-451], whereas others have not observed this phenomenon. We have resolved this long-running literature debate and shown unequivocally that this difference in reported behaviour can be attributed to differences in the preparation of ( S )-ASA used by each researcher. DHDPS is not inhibited by its substrate; rather, the inhibition is due to an, as yet, unidentified inhibitor in preparations of the substrate generated by ozonolysis. Furthermore, we demonstrate that ( R )-ASA is neither an inhibitor nor a substrate of DHDPS from Escherichia coli.
Dobson
Renwick C J
RC
School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
Gerrard
Juliet A
JA
Pearce
F Grant
FG
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D050746:Dihydrodipicolinate Reductase; D004791:Enzyme Inhibitors / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000302:isolation & purification; D013237:Stereoisomerism; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D001224:Aspartic Acid; C006644:aspartic semialdehyde; D050746:Dihydrodipicolinate Reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase