Synechococcus mutants resistant to an enamine mechanism inhibitor of glutamate-1-semialdehyde aminotransferase.
An enamine mechanism-based inactivator of mammalian delta-aminobutyric acid aminotransferase, 4-amino 5-fluoropentanoic acid is a potent inhibitor of cell growth and pigment formation in the cyanobacterium Synechococcus PCC 6301. It was demonstrated that 4-amino 5-fluoropentanoic acid inhibits the aminolaevulinate synthesis at glutamate 1-semialdehyde aminotransferase and that in the mutant obtained by exposing cells to 40 microM 4-amino 5-fluoropentanoic acid, this enzyme was insensitive to the inhibitor. The specific activity of glutamate 1-semialdehyde aminotransferase in cell extracts was lower in the mutant, although the cell growth rate was unaffected. The decrease in sensitivity to 4-amino 5-fluoropentanoic acid in the mutant is due to a structural gene mutation, a single base change in the hemL gene resulting in a S162T substitution in the gene product.
Bishop
K
K
Institute of Biological Sciences, University of Wales, Aberystwyth, Penglais, UK.
Gough
K
K
Mahoney
S
S
Smith
A
A
Rogers
L
L
D000622:Aminolevulinic Acid / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002734:Chlorophyll / Q000378:metabolism; D000458:Cyanobacteria / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D009154:Mutation; D010421:Pentanoic Acids / Q000494:pharmacology*; D017422:Sequence Analysis, DNA
D004791:Enzyme Inhibitors; D010421:Pentanoic Acids; D002734:Chlorophyll; C032606:4-amino-5-fluoropentanoic acid; D000622:Aminolevulinic Acid; D019751:Intramolecular Transferases; C061049:glutamate-1-semialdehyde 2,1-aminomutase