BIOL 88 |
| The plasma form of human platelet activating factor acetylhydrolase (pPAF-AH) functions by reducing PAF levels as a general anti-inflammatory scavenger and is linked to anaphylactic shock, asthma and allergic reactions. In addition to the role in reducing PAF levels, enzyme has also been implicated in hydrolytic activities of other pro-inflammatory agents, such as oxidized lipids. Physiologically, this enzyme is found associated to LDL particles and is considered an interfacial enzyme. Moreover, pPAFAH has been shown to be reactive with organophosphate insecticides and nerve agents. pPAFAH belongs to a subfamily of phospholipase A2 that removes the acetyl group at sn-2 position of phospholipids. Here we present the crystal structure of pPAFAH of molecular mass 42 KDa, a truncation of the 47 KDa form. The structure of this enzyme has been solved from data collected to resolution of 1.4 Angstroms after SAD-phasing from the Hg-derivative data to 2.7 Angstroms. It has a typical ?/? hydrolase fold and consists of a trypsin-like catalytic triad (S273, D296 and H351). C-terminus region is negatively charged due to the presence of an acidic patch and believed to be the potential force of binding to the LDL interface in human blood plasma, which drives catalytic activity of this enzyme. Mutational study of some C-terminal charged residues of the enzyme and its binding to the LDL will be discussed. Crystallographic analysis of complex of this enzyme after covalent modification of the active site Ser residue by organophosphates (para-oxon, sarin, soman and tabun) will also be discussed. |
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Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |