Phospholipase A2: Difference between revisions

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Alexander Berchansky, Michal Harel, Jaime Prilusky, Joel L. Sussman

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 <scene name='Journal:FLS:1/Cv/4'>Curcumin</scene> possesses anti-inflammatory activity. The binding of curcumin with PLA<sub>2</sub> was studied using X-ray crystallography. Since the electron density found in the active site did not match with curcumin, <scene name='Journal:FLS:1/Cv/5'>2-methoxycyclohexa-2-5-diene-1,4-dione (MCW)</scene> (the photo-degraded product of curcumin) <scene name='Journal:FLS:1/Cv/6'>was fitted</scene> in the unexplained electron density. To understand the <scene name='Journal:FLS:1/Cv/9'>binding mode of actual curcumin</scene>, molecular docking studies was carried out. <scene name='Journal:FLS:1/Cv/10'>Both crystallographic and docked structures were superimposed</scene>  with respect to the ligand position and identified that <scene name='Journal:FLS:1/Cv/13'>curcumin is binding in the hydrophobic cavity</scene> of PLA<sub>2</sub> with a binding energy -16.81 Kcal/mol. The binding mode is in such a manner that it can prevent the entry of substrate to the hydrophobic active site. These studies indicate that curcumin can be act as an inhibitor to PLA<sub>2</sub>.
+== '''Interaction of Atropine with Phospholipase 2A''' ==
+<scene name='42/420811/Cv/1'>Atropine in complex with phospholipase A2</scene> ([[1th6]]).
+[[Image:Phospholipase A2.gif|thumb|left|350px|Phospholipase 2A in complex with cell membrane]]
+{{Clear}}
+In addition to its ability to form complexes with acetylcholine receptors, atropine can also complex with phospholipase A2. Phospholipase A2 is a category of heat-stable enzymes which are involved in cell signaling processes, such as the inflammatory response. <ref>Kumar, Jainendra; Bala, Priti; Vihwal, Preeti. ''Analysis of Interaction of atropine with phospholipase A2 (1th6.pdb)''. Department of Botany and Biotechnlogy, College of Commerce, Patna, India.</ref>. Phospholipase 2A is an upstream regulator of inflammatory processes, and more specifically, it recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing lysophospholipids <ref> Phospholipase A2. http://www.worldlingo.com/ma/enwiki/en/Phospholipase_A2 </ref>.
+This protein is found in mammals, reptile venom, and bacteria. In humans, the overproduction of phospholipase A2 leads to neurologic disorders such as schizophrenia and possibly autism <ref> Phospholipase A2. http://www.worldlingo.com/ma/enwiki/en/Phospholipase_A2 </ref>. An inhibitor of Phospholipase A2, such as Atropine, could be used to treat disorders associated with neural trauma, since Phospholipase A2 increases inflammation which could be potentially complicate neural trauma cases <ref> Phospholipase A2. http://www.worldlingo.com/ma/enwiki/en/Phospholipase_A2 </ref>.
+The image to the above shows the membrane-bound phospholipase A2 in blue <ref> pla2. http://www.ks.uiuc.edu/Research/smd_imd/pla2/pla2.gif </ref>.
+=== '''Atropine in the Active Site of Phospholipase 2A''' ===
+Atropine is an inhibitor of phospholipase 2A, and can be seen in complex with this enzyme on the left. The <scene name='Sandbox_53/Atropine_structure/1'>structure of atropine</scene> can be seen more clearly in gray using the ball-and stick representation of the drug and protein. It can also be seen in green in this <scene name='Sandbox_53/Phospholipase2a_composition/1'>space-filling model</scene>, where protein appears in brown, ligands appear in green, and solvents appear in blue. Finally, the
+<scene name='Sandbox_53/Phospholipase2a_rainbow/1'>N to C terminal</scene> portions of the protein can be highlighted from blue to red in a rainbow, and the active site with atropine can be seen in the middle of the protein.
+Atropine interacts with phospholipase 2A at residues asp29 and tyr49 on the protein. The
+<scene name='Sandbox_53/Phospholipase2a_residues/1'>residues</scene> of atropine interacting with phospholipase 2A can be seen on the right. The amino acid residues in the active site are labeled. As seen in the acetylcholine receptor, the <scene name='Sandbox_53/Phospholipase_hyrophobic/1'>hydrophobic</scene> regions of the phospholipase 2A enzyme are found in the active site, which is where the atropine binds and inhibits the enzyme. The hydrophobic regions, represented in gray, can be seen surrounding atropine, which is positioned in the active site and capped by red oxygen atoms.
+Removing the labels, atropine can be seen making contact with the atoms emphasized by the space filling model, interacting with the <scene name='Sandbox_53/Phospholipase2a_interactions/1'>active site</scene> of phospholipase 2A through white as-tricks.
 </StructureSection>