Insecticidal toxins from the bacterium Photorhabdus luminescens : gene cloning and toxin histopathology

✍ Scribed by Bowen, David; Blackburn, Michael; Rocheleau, Thomas A; Andreev, Olga; Golubeva, Elena; ffrench-Constant, Richard H

• Book ID: 101215578
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 199 KB
• Volume: 55
• Category: Article
• ISSN: 1526-498X
• DOI: 10.1002/(sici)1096-9063(199906)55:6<666::aid-ps5>3.0.co;2-g

✦ Synopsis

Naturally occurring, biologically active compounds provide valuable tools for elucidating the molecular basis of physiological events. In the present study, 28 picrotoxane terpenoids, including picrodendrins (Fig 1 ) 1,2 isolated from the Euphorbiaceae plant, Picrodendron baccatum (L) Krug & Urban, have been evaluated for their ability to inhibit speci®c binding of [ 3 H]1-(4-ethynylphenyl)-4-propyl-2,6,7-trioxabicyclo[2.2.2.]octane (EBOB), the noncompetitive antagonist of ionotropic GABA receptors, to rat-brain and house¯y-head membranes. 3 Picrodendrin Q was the most potent competitive inhibitor, with IC 50 values of 16 nM (rat) and 22 nM (house¯ies). The spiro g-butyrolactone moiety, containing a carbonyl group conjugated with an unsaturated bond at the 13-position and the hydrophobic substituents at the 4-position play important roles in the interaction of picrodendrins with their binding site in rat GABA receptors. In contrast, such structural features are not strictly required in the case of the interaction with house¯y GABA receptors; the spiro g-butyrolactone, bearing the 16-sp 3 carbon atom at the 13-position and hydroxyl groups at various positions are somewhat tolerated.

Quantitative structure±activity studies have clearly shown that the electronegativity of the 16-carbon atom and the presence or absence of the 4-and 8-hydroxyl groups are important determinants of potency of norditerpenes in house¯y receptors, while the negative charge on the 17-carbonyl oxygen atom is likely to be important in the case of rat receptors. These ®ndings are consistent with those of our previous studies 4 that there are signi®cant differences in the structures of their binding site between rat and house¯y GABA receptors.