Inhibition of bacterial aminopropyltransferases by S-adenosyl-1,8-diamino-3-thiooctane and by dicyclohexylamine

Anthony E. Pegg, Alan J. Bitonti, Peter P. McCann, James K. Coward

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Bacterial aminopropyltransferases from Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa were strongly inhibited by S-adenosyl-1,8-diamino-3-thiooctane (AdoDATO) and by dicyclohexylamine. The sensitivity to these drugs in vitro was comparable to that of mammalian spermidine synthase, but AdoDATO was much less potent in reducing spermidine content in the bacteria than in mammalian cells. Although AdoDATO was a stronger inhibitor than dicyclohexylamine in vitro, dicyclohexylamine was more active in reducing bacterial spermidine levels in vivo, suggesting that it is take up better or is more stable in the cell and is the preferable compound for in vivo studies in microorganisms. The strong inhibition of spermidine synthases by AdoDATO which is a transition state analog supports the concept that these enzymes proceed by a single displacement reaction, rather than by a ping-pong mechanism.

Original languageEnglish (US)
Pages (from-to)192-196
Number of pages5
JournalFEBS Letters
Volume155
Issue number2
DOIs
StatePublished - May 8 1983

Fingerprint

Spermidine Synthase
Spermidine
Serratia marcescens
Microorganisms
Pseudomonas aeruginosa
Escherichia coli
Bacteria
Cells
dicyclohexylamine
S-adenosyl-3-thio-1,8-diaminooctane
Enzymes
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Pegg, Anthony E. ; Bitonti, Alan J. ; McCann, Peter P. ; Coward, James K. / Inhibition of bacterial aminopropyltransferases by S-adenosyl-1,8-diamino-3-thiooctane and by dicyclohexylamine. In: FEBS Letters. 1983 ; Vol. 155, No. 2. pp. 192-196.
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Inhibition of bacterial aminopropyltransferases by S-adenosyl-1,8-diamino-3-thiooctane and by dicyclohexylamine. / Pegg, Anthony E.; Bitonti, Alan J.; McCann, Peter P.; Coward, James K.

In: FEBS Letters, Vol. 155, No. 2, 08.05.1983, p. 192-196.

Research output: Contribution to journalArticle

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T1 - Inhibition of bacterial aminopropyltransferases by S-adenosyl-1,8-diamino-3-thiooctane and by dicyclohexylamine

AU - Pegg, Anthony E.

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AB - Bacterial aminopropyltransferases from Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa were strongly inhibited by S-adenosyl-1,8-diamino-3-thiooctane (AdoDATO) and by dicyclohexylamine. The sensitivity to these drugs in vitro was comparable to that of mammalian spermidine synthase, but AdoDATO was much less potent in reducing spermidine content in the bacteria than in mammalian cells. Although AdoDATO was a stronger inhibitor than dicyclohexylamine in vitro, dicyclohexylamine was more active in reducing bacterial spermidine levels in vivo, suggesting that it is take up better or is more stable in the cell and is the preferable compound for in vivo studies in microorganisms. The strong inhibition of spermidine synthases by AdoDATO which is a transition state analog supports the concept that these enzymes proceed by a single displacement reaction, rather than by a ping-pong mechanism.

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