title: Zinc and barium inhibit the phospholipase A2 from Naja naja atra by different mechanisms.
abstract: The mode of inhibition of the phospholipase A2 (PLA2) enzyme from the Chinese cobra (Naja naja atra) by Zn2+ is qualitatively different from inhibition by Ba2+. Inhibition by Ba2+ shows the kinetic characteristics of a conventional competitive inhibitor acting to displace Ca2+ from a single essential site, but Zn2+ has the paradoxical property of being more inhibitory at high than at low Ca2+ concentration. Kinetic analysis of the Ca(2+)-dependence of enzymic activity shows a bimodal response, indicating the presence of two Ca(2+)-binding sites with affinities of 2.7 microM and 125 microM respectively, and we propose that these can be identified with the two Ca(2+)-binding sites revealed by crystallographic analysis [White, Scott, Otwinowski, Gleb and Sigler (1990) Science 250, 1560-1563]. The results are consistent with the model that the enzyme is activated by two Ca2+ ions, one that is essential and can be displaced by Ba2+, and one that modulates the activity by a further 5-10-fold and which can be displaced by Zn2+. An alternative model is also presented in which the modulating Zn(2+)-binding site is a phenomenon of the lipid/water interface.
authors.affiliation: Department of Cell Biology, University of Glasgow, Scotland.
authors.forename: M
authors.initials: M
authors.lastname: Mezna
authors.forename: T
authors.initials: T
authors.lastname: Ahmad
authors.forename: S
authors.initials: S
authors.lastname: Chettibi
authors.forename: D
authors.initials: D
authors.lastname: Drainas
authors.forename: A J
authors.initials: AJ
authors.lastname: Lawrence
mesh_terms: D001464:Barium / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004546:Elapid Venoms / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D015032:Zinc / Q000494:pharmacology*
chemical_list: D004546:Elapid Venoms; D007527:Isoenzymes; D001464:Barium; D010741:Phospholipases A; D054467:Phospholipases A2; D015032:Zinc; D002118:Calcium