Phospholipase A2 complexes

Hershberg, R. D., Reed, G. H., Slotboom, A. J., and de Haas, G. H. (1976). Phospholipase A2 complexes with gadolinium (III) and interaction of the enzyme-metal ion complex with monomeric and micellar alkylphosphorylcholines. Water proton nuclear magnetic relaxation studies. Biochemistry 15,2268-2274. 

Although extraction of lipids from membranes can be induced in atomic force apparatus (Leckband et al., 1994) and biomembrane force probe (Evans et al., 1991) experiments, spontaneous dissociation of a lipid from a membrane occurs very rarely because it involves an energy barrier of about 20 kcal/mol (Cevc and Marsh, 1987). However, lipids are known to be extracted from membranes by various enzymes. One such enzyme is phospholipase A2 (PLA2), which complexes with membrane surfaces, destabilizes a phospholipid, extracts it from the membrane, and catalyzes the hydrolysis reaction of the srir2-acyl chain of the lipid, producing lysophospholipids and fatty acids (Slotboom et al., 1982 Dennis, 1983 Jain et al., 1995). SMD simulations were employed to investigate the extraction of a lipid molecule from a DLPE monolayer by human synovial PLA2 (see Eig. 6b), and to compare this process to the extraction of a lipid from a lipid monolayer into the aqueous phase (Stepaniants et al., 1997). 

Subscript (ads) denotes adsorption via a thiolate linkage, while (ps) stands for a physisorbed and/or adsorbed state via different interactions. However, large dimensions of the studied molecules and their amphiphilic nature make the surface reaction mechanism more complex than in case of cystine/cysteine. Interfacial microstructure plays an important role in the determination of the surface behavior of the adsorbed molecules. From the study on the charge-transfer kinetics, the transfer coefficient a was calculated as slightly less than 0.50, while the rate constant (based on Laviron s derivations [105]) was of the order of 10 s k The same authors [106] have shown earlier that the adsorption rate constant of porcine pancreatic phospholipase A2 at mercury via one of its disulfide groups is of the order of 10 s h... 

White, S.P., Scott, D.L., Otwinowski, Z., Gelb, M.H. und Sigler, P.B. Crystal structure of Cobra phospholipase A2 in a complex with a transition state analogue (1990) Science 250, 1560-1566... 

Sponge-derived sesterterpenoids are potent anti-inflammatory metabolites which inhibit phospholipase A2 (Sipkema et ah, 2005a). In arachi-donic acid pathway of inflammatory response (Fig. 8.3), phospholipase A2 catalyzes the release of membrane-bound phospholipids to produce inflammatory mediators once stimulated by tissue injury. Manoalide (Fig. 8.4) is a best known sponge-derived anti-inflammatory sesterterpe-noid. Dysidotronic acid (Fig. 8.5), non-complex manoalide analogue, has been identified as an anti-inflammatory metabolite of the sponge Dysidea sp. The mechanism by which dysidotronic acid inhibit inflammation is much more selective and potent than manoalide. This sesquiterpenoid... 

K Kitadokoro, S Hagishita, T Sato, M Ohtani, K Miki. Crystal structure of human secretory phospholipase A2-IIA complex with the potent indolizine inhibitor 120-1032. J Biochem (Tokyo) 123 619-623, 1998. 

Kurrasch-Orbaugh DM, Parrish JC, Watts VJ, Nichols DE. A complex signaling cascade links the serotonin2A receptor to phospholipase A2 activation the involvement of MAP kinases. J Neurochem 2003 86 980-991. 

Crystal Structure of the Complex of Bovine Pancreatic Phospholipase A2 with the Inhibitor l-Hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol. 

Arachidonic acid, a 20-carbon fatty acid, is the primary precursor of the prostaglandins and related compounds (see Figure 39.3). Arachidonic acid is present as a component of the phospholipids of cell membranes, primarily phosphatidyl inositol and other complex lipids.1 Free arachidonic acid is released from tissue phospholipids by the action of phospholipase A2 and other acyl hydrolases, via a process controlled by hormones and other stimuli (see Figure 39.3). There are two major pathways in the synthesis of the eicosanoids from arachidonic acid (see Figure 39.3). 

The release of arachidonic acid from these lipids by the synchronised activation of phospholipase C/phospholipase A2 could occur in complexes of proteins that are... 

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