Bacterial 5-n-alkyl(C19–C25) resorcinols are non-competitive inhibitors of phospholipase A2
K. Yu. Gordeev, V. V. Bitkov, N. N. Pridachina, V. A. Nenashev, S. G. Batrakov
Research Laboratory of Biologically Active Substances of Hydrobionts, Ministry of Public Health of the USSR, Moscow
Abstract: 5-n-Alkyl(C19–C25) resorcinols (AR), which are the major cell lipids of the nitrogen-fixing bacterium Azotobacter chroococcum, are found to inhibit the hydrolysis of phospati-dylcholine (PC) catalyzed by the cobra venom (Naja naja oxiana) phospholipase A2 in both diethyl ether solution and bimolecular lipid membranes (BLM). In the phospholipase A2-containing aqueous medium, the BLM could be formed from a mixture of PC and AR provided that AR content was at least 30 mol. %. Life-time of the bilayer extended with the increase of AR percentage in the parent lipid mixture. Measurements of the conductivity of the BLM prepared from AR alone in the presence or otherwise of the enzyme revealed association between AR and phospholipase A2. Inhibition of the PC hydrolysis in the ether solution depended substantially on the AR/enzyme ratio but only slightly on the PC concentration. The inhibitory effect of mono-O-methylated AR on the same reaction was much weaker than of AR itself either in ether solution or in the BLM. Therefore this effect may well be attributed to “dilution” of the substrate on the surface, where it comes in contact with the enzyme. The observed effect of AR is assumed to be due to their non-specific binding to the phospholipase A2 molecules, with an AR molecule combining with two sites of the protein thus giving rise to its conformational modification.
Russian Journal of Bioorganic Chemistry 1991, 17 (10):1357-1364