Inhibitory effect of modified bafilomycins and concanamycins on P- and V-type adenosinetriphosphatases

Biochemistry. 1993 Apr 20;32(15):3902-6. doi: 10.1021/bi00066a008.

Abstract

Various ATPases have been tested for their sensitivity to naturally occurring unusual macrolides and their chemically modified derivatives, which are structurally related to bafilomycin A1 (1), the first specific inhibitor of vacuolar ATPases. The structure-activity study showed that in general the concanamycins, 18-membered macrolides, are better and more specific inhibitors than the bafilomycins of this class of membrane-bound ATPases. The additional carbohydrate residue is not responsible for the improved activity. The importance of an intact hemiketal ring, which is part of an intramolecular hydrogen-bonding network, and the effects of the size of the macrolactone ring are discussed. The structurally related elaiophylin (13), a C2-symmetric macrodiolide antibiotic, proved to be inactive on vacuolar ATPases but still retained its inhibitory effect on P-type ATPases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Synthetase Complexes
  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Anti-Bacterial Agents / pharmacology*
  • Cation Transport Proteins*
  • Escherichia coli / enzymology
  • Escherichia coli Proteins*
  • Macrolides*
  • Multienzyme Complexes / antagonists & inhibitors
  • Neurospora crassa / enzymology
  • Phosphotransferases / antagonists & inhibitors
  • Proton-Translocating ATPases / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Cation Transport Proteins
  • Escherichia coli Proteins
  • Macrolides
  • Multienzyme Complexes
  • concanamycin A
  • concanamycin C
  • bafilomycin A1
  • Phosphotransferases
  • ATP Synthetase Complexes
  • Adenosine Triphosphatases
  • potassium translocating Kdp-ATPase, E coli
  • potassium transporting ATPase
  • Proton-Translocating ATPases