Biochemical bases for the antimetabolite action of L-serine hydroxamate.
The amino acid analogue l-serine hydroxamate, which is bacteriostatic for Escherichia coli, has been shown to inhibit protein synthesis. The antimetabolite is a competitive inhibitor of seryl-transfer ribonucleic acid (tRNA) synthetase with a K(i) value of 30 mum. Mutants resistant to l-serine hydroxamate have been selected, and three were shown to have seryl-tRNA synthetases with increased K(i) values. One mutant contains a 3-phosphoglycerate dehydrogenase which is insensitive to inhibition by l-serine.
D001426:Bacterial Proteins / Q000096:biosynthesis; D002247:Carbon Isotopes; D003470:Culture Media; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D005827:Genetics, Microbial; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008025:Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009153:Mutagens; D009154:Mutation; D009604:Nitrosoguanidines; D012329:RNA, Bacterial / Q000096:biosynthesis; D012694:Serine / Q000378:metabolism / Q000494:pharmacology*; D013053:Spectrophotometry; D013237:Stereoisomerism; D013912:Threonine / Q000378:metabolism; D014316:Tritium; D014461:Ultracentrifugation; D014498:Uracil / Q000378:metabolism
D001426:Bacterial Proteins; D002247:Carbon Isotopes; D003470:Culture Media; D006877:Hydroxamic Acids; D009153:Mutagens; D009604:Nitrosoguanidines; D012329:RNA, Bacterial; D014316:Tritium; D013912:Threonine; D012694:Serine; D014498:Uracil; D005993:Glycerolphosphate Dehydrogenase; D008025:Ligases; D007930:Leucine; D005998:Glycine