Skip to main content
NCBI home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1971 Jun;106(3):972–982. doi: 10.1128/jb.106.3.972-982.1971

Biochemical Bases for the Antimetabolite Action of l-Serine Hydroxamate

Tetsuya Tosa a,1, Lewis I Pizer a
PMCID: PMC248741  PMID: 4934072

Abstract

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 Ki value of 30 μm. Mutants resistant to l-serine hydroxamate have been selected, and three were shown to have seryl-tRNA synthetases with increased Ki values. One mutant contains a 3-phosphoglycerate dehydrogenase which is insensitive to inhibition by l-serine.

Full text

PDF
972

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. DIXON M. The determination of enzyme inhibitor constants. Biochem J. 1953 Aug;55(1):170–171. doi: 10.1042/bj0550170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. EIDLIC L., NEIDHARDT F. C. PROTEIN AND NUCLEIC ACID SYNTHESIS IN TWO MUTANTS OF ESCHERICHIA COLI WITH TEMPERATURE-SENSITIVE AMINOACYL RIBONUCLEIC ACID SYNTHETASES. J Bacteriol. 1965 Mar;89:706–711. doi: 10.1128/jb.89.3.706-711.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Eagle H., Washington C. L., Levy M. End product control of amino acid synthesis by cultured human cells. J Biol Chem. 1965 Oct;240(10):3944–3950. [PubMed] [Google Scholar]
  4. Folk W. R., Berg P. Isolation and partial characterization of Escherichia coli mutants with altered glycyl transfer ribonucleic acid synthetases. J Bacteriol. 1970 Apr;102(1):193–203. doi: 10.1128/jb.102.1.193-203.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. HOAGLAND M. B., KELLER E. B., ZAMECNIK P. C. Enzymatic carboxyl activation of amino acids. J Biol Chem. 1956 Jan;218(1):345–358. [PubMed] [Google Scholar]
  6. Hirsh D. I., Lipmann F. The divergence in reactivity of aminoacyl transfer ribonucleic acid synthetases of Escherichia coli with hydroxylamine. J Biol Chem. 1968 Nov 10;243(21):5724–5730. [PubMed] [Google Scholar]
  7. KURLAND C. G., MAALOE O. Regulation of ribosomal and transfer RNA synthesis. J Mol Biol. 1962 Mar;4:193–210. doi: 10.1016/s0022-2836(62)80051-5. [DOI] [PubMed] [Google Scholar]
  8. Katze J. R., Konigsberg W. Purification and properties of seryl transfer ribonucleic acid synthetase from Escherichia coli. J Biol Chem. 1970 Mar 10;245(5):923–930. [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Norton S. J., Chen Y. T. Beta-aspartylhydroxamic acid: its action as a feedback inhibitor and a repressor of asparagine synthetase in Lactobacillus arabinosus. Arch Biochem Biophys. 1969 Feb;129(2):560–566. doi: 10.1016/0003-9861(69)90215-x. [DOI] [PubMed] [Google Scholar]
  11. PIZER L. I. THE PATHWAY AND CONTROL OF SERINE BIOSYNTHESIS IN ESCHERICHIA COLI. J Biol Chem. 1963 Dec;238:3934–3944. [PubMed] [Google Scholar]
  12. RICHMOND M. H. The effect of amino acid analogues on growth and protein synthesis in microorganisms. Bacteriol Rev. 1962 Dec;26:398–420. doi: 10.1128/br.26.4.398-420.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Regan J. D., Vodopick N., Takeda S., Lee W. H., Faulcon F. M. Serine requirement in leukemic and normal blood cells. Science. 1969 Mar 28;163(3874):1452–1453. doi: 10.1126/science.163.3874.1452. [DOI] [PubMed] [Google Scholar]
  14. STENT G. S., BRENNER S. A genetic locus for the regulation of ribonucleic acid synthesis. Proc Natl Acad Sci U S A. 1961 Dec 15;47:2005–2014. doi: 10.1073/pnas.47.12.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Smith H. S., Pizer L. I. Abortive infection of Escherichia coli strain W by T2 bacteriophage. J Mol Biol. 1968 Oct 14;37(1):131–149. doi: 10.1016/0022-2836(68)90078-8. [DOI] [PubMed] [Google Scholar]
  16. Sugimoto E., Pizer L. I. The mechanism of end product inhibition of serine biosynthesis. I. Purification and kinetics of phosphoglycerate dehydrogenase. J Biol Chem. 1968 May 10;243(9):2081–2089. [PubMed] [Google Scholar]
  17. Sundharadas G., Katze J. R., Söll D., Konigsberg W., Lengyel P. On the recognition of serine transfer RNA's specific for unrelated codons by the same seryl-transfer RNA synthetase. Proc Natl Acad Sci U S A. 1968 Oct;61(2):693–700. doi: 10.1073/pnas.61.2.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. UMBARGER H. E., UMBARGER M. A., SIU P. M. BIOSYNTHESIS OF SERINE IN ESCHERICHIA COLI AND SALMONELLA TYPHIMURIUM. J Bacteriol. 1963 Jun;85:1431–1439. doi: 10.1128/jb.85.6.1431-1439.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES