Effect of analogues of diaminopimelic acid on the meso-diaminopimelate-adding enzyme from Escherichia coli.
Several analogues of diaminopimelic acid (A2pm) were tested as substrates or inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coli. They included lanthionine derivatives, a phosphonic analogue, heterocyclic compounds, 3-fluoro-A2pm, 4-methylene-A2pm and N-hydroxy-A2pm. The best substrates were, in decreasing order of specific enzyme activity, (2S,3R,6S)-3-fluoro-A2pm, meso-lanthionine sulfoxide and N-hydroxy-A2pm (mixture of stereoisomers). In those cases where all the stereoisomers were available, the specificity could be described as meso > > DD approximately to LL. N-Hydroxy-A2pm (mixture of stereoisomers) strongly inhibited the addition of radioactive meso-A2pm to UDP-N-acetylmuramoyl-dipeptide.
Auger
G
G
URA 1131 du CNRS, Biochimie Moléculaire et Cellulaire, Université de Paris-Sud, Orsay, France.
van Heijenoort
J
J
Vederas
J C
JC
Blanot
D
D
D003960:Diaminopimelic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D010453:Peptide Synthases / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D003960:Diaminopimelic Acid; D010453:Peptide Synthases; C049145:UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase