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

FEBS Letters

McCann, Peter P.²  Bitonti, Alan J.²  Coward, James K.¹  Pegg, Anthony E.³ 

[1] Department of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12181, USA;Merrell Dow Research Center, 2110 E. Galbraith Road, Cincinnati OH, 45215, USA;Department of Physiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033, USA

关键词: Spermidine biosynthesis;    Polyamine;    Aminopropyltransferase mechanism;    Bacterial growth;   

DOI  :  10.1016/0014-5793(82)80600-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown