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*'''Pro-phosphlipase (PPLA2)''' is a pancreatic PLA2 whose 7-mer N-terminal peptide is cleaved off to produce the active PLA2.<br />
*'''Pro-phosphlipase (PPLA2)''' is a pancreatic PLA2 whose 7-mer N-terminal peptide is cleaved off to produce the active PLA2.<br />
*For details on Lys49 snake-venom PLA2 see [[Anum-II]].<br />
*For details on Lys49 snake-venom PLA2 see [[Anum-II]].<br />
*For PLA2 inhibitor see [[Atropine]]<br />
*See also [[Phospholipase (Hebrew)]].
*See also [[Phospholipase (Hebrew)]].


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PLA2 serve as pharmacological targets for therapeutical treatment of diseases like atherosclerosis, immune disorders, cardiovascular diseases and cancer<ref>PMID:24907600</ref>.  Reduced Lp-PLA2 activity is observed in patients with severe sepsis.  There is association between the level of Lp-PLA2 in plasma and the risk of future cardiovascular events<ref>PMID:19272461</ref>.  
PLA2 serve as pharmacological targets for therapeutical treatment of diseases like atherosclerosis, immune disorders, cardiovascular diseases and cancer<ref>PMID:24907600</ref>.  Reduced Lp-PLA2 activity is observed in patients with severe sepsis.  There is association between the level of Lp-PLA2 in plasma and the risk of future cardiovascular events<ref>PMID:19272461</ref>.  


==Diclofenac binding to Phospholipase A2<ref>PMID:PMID:25237841</ref>==
==Diclofenac binding to Phospholipase A2<ref>PMID:16552142</ref>==
'''Abstract from Pubmed'''
'''Abstract from Pubmed'''


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shows three mail helices in phospholipase A2.  
shows three mail helices in phospholipase A2.  
The <scene name='Diclofenac_binding_to_Phospholipase_A2/Active_site/2'>active site residues</scene> are His 48, Asp 49, Tyr 52 and Glu 99 in the structure.  
The <scene name='Diclofenac_binding_to_Phospholipase_A2/Active_site/2'>active site residues</scene> are His 48, Asp 49, Tyr 52 and Glu 99 in the structure.  
Diclofenac makes several <scene name='Diclofenac_binding_to_Phospholipase_A2/Hydro/1'>Hydrophobic interactions</scene> with the substrate binding site of enzyme. ligand binding is shown in <scene name='Diclofenac_binding_to_Phospholipase_A2/Space_filling/1'>space filling</scene> model of the complex.
Diclofenac makes several <scene name='Diclofenac_binding_to_Phospholipase_A2/Hydro/1'>Hydrophobic interactions</scene> with the substrate binding site of enzyme. ligand binding is shown in <scene name='Diclofenac_binding_to_Phospholipase_A2/Space_filling/1'>space filling</scene> model of the complex. See also [[Diclofenac]].


== Crystal structure of porcine pancreatic phospholipase A<sub>2</sub> in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione ==
== Crystal structure of porcine pancreatic phospholipase A<sub>2</sub> in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione ==
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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>.
<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>.
</StructureSection>


== 3D Structures of Phospholipase A2 ==
== '''Interaction of Atropine with Phospholipase A2''' ==


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
<scene name='42/420811/Cv/1'>Atropine in complex with phospholipase A2</scene> ([[1th6]]).
{{#tree:id=OrganizedByTopic|openlevels=0|


*Phospholipase A2  
[[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>.


**[[1une]], [[1mkt]], [[1irb]], [[1bp2]], [[1bpq]], [[1g4i]], [[2bp2]], [[2bpp]] - bPLA2 – bovine<br />
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>.
**[[2zp3]], [[2zp4]], [[2zp5]], [[1c74]], [[1kvw]], [[1kvx]], [[1kvy]], [[1ceh]], [[1mks]], [[1mku]], [[1vkq]], [[1vl9]], [[2bax]], [[2bch]], [[2bd1]], [[1o3w]], [[1gh4]] – bPLA2 (mutant) – bovine<br />
**[[1bvm]] – bPLA2 - NMR<br />
**[[1qll]], [[2q2j]] – PLA2 – ''Bothrops pirajai''<br />
**[[2qog]] – PLA2 – ''Crotalus durissus''<br />
**[[2ph4]] – PLA2 – ''Zhaoermia mangshanensis''<br />
**[[2h4c]], [[1q6v]] – IvPLA2 – Indian viper<br />
**[[1vpi]] – PLA2 – sand viper<br />
**[[2osn]], [[1fe5]], [[1dpy]] – kPLA2 – krait<br />
**[[1g0z]], [[1g2x]] – kPLA2 (mutant)<br />
**[[2wg7]], [[2wg8]] – rPLA2 – rice<br />
**[[1p2p]], [[4p2p]] – pPLA2 - pig<br />
**[[1y6p]], [[2phi]], [[3p2p]]  – pPLA2 (mutant) – pig<br />
**[[1sfv]], [[1sfw]], [[1pir]], [[1pis]] – pPLA2 - NMR<br />
**[[1yxh]] – NsPLA2 – ''Naja sagittifera''<br />
**[[1oz6]], [[2qhe]] – PLA2 – ''Echis carinatus''<br />
**[[1it4]], [[1it5]] – PLA2 – Stretomyces violaceoruber – NMR<br />
**[[1mg6]] – PLA2 – ''Agkistrodon acutus''<br />
**[[1s8g]], [[1s8h]], [[1s8i]] – PLA2 – copperhead<br />
**[[1ijl]] – PLA2 – ''Deinagkistrodon acutus''<br />
**[[1mc2]], [[4hg9]] – PLA2 – Chinese moccasin<br />
**[[1c74]], [[1kvw]], [[1kvx]], [[1kvy]], [[1ceh]] – bPLA2 (mutant) – bovine<br />
**[[1b4w]], [[1jia]], [[1c1j]] – AhPLA2 - ''Agkistrodon halys''<br />
**[[1a2a]], [[1m8r]], [[1m8s]], [[1psj]] – PLA2 – ''Gloydius halys''<br />
**[[1a3d]], [[1a3f]], [[1ln8]], [[1mh2]], [[1mh8]], [[1ows]], [[1poa]], [[1psh]], [[1s6b]], [[1sz8]], [[1xxw]], [[1y75]], [[1yxl]], [[1yxh]] – PLA2 – ''Naja naja''<br />
**[[1mh7]] - PLA2 – ''Naja sagittifera''<br />
**[[2osh]] – PLA2 – Chinese cobra<br />
**[[1ae7]], [[2not]], [[4e4c]] – PLA2 – ''Notechis scutatus''<br />
**[[1aok]], [[1jlt]], [[1q5t]], [[1rgb]], [[3dih]], [[3g8g]], [[3g8h]] – PLA2 – ''Vipera ammodytes''<br />
**[[2i0u]] – PLA2 – ''Vipera nikolskii''<br />
**[[1ayp]], [[1bbc]], [[1pod]] – hPLA2 – human<br />
**[[1rlw]] – hPLA2 CALB domain<br />
**[[1faz]], [[1kp4]] – PLA2 – ''Streptomyces violaceruber''<br />
**[[1god]] – PLA2 – ''Cerrophidion godmani''<br />
**[[1gp7]], [[1m8t]] – PLA2 – ''Ophiophagus hanna''<br />
**[[1ozy]], [[1p7o]], [[1pwo]] – PLA2 – ''Micropechis ikahena''<br />
**[[1pp2]] – PLA2 – rattlesnake<br />
**[[1ppa]], [[1vap]] – PLA2 – cottonmouth<br />
**[[1u4j]] – PLA2 – ''Bungarus caeruleus''<br />
**[[2aoz]] – PLA2 – ''Atropoides nummifer''<br />
**[[3v9m]] – PLA2 – king brown snake<br />


*Phospholipase A2 group I
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>.


**[[3elo]] – hPLA2G1B<br />
=== '''Atropine in the Active Site of Phospholipase A2''' ===
**[[3q4y]] - PLA2G1 - Andaman cobra <br />
**[[3fvi]], [[3fvj]] – pPLA2G1B+octyl sulfate<br />
**[[3qlm]] - pPLA2G1B + hexadecanoic acid<br />
**[[3l30]], [[4dbk]] - pPLA2G1B+berberine derivative<br />
**[[4g5i]] – pPLA2 + DBP<br />
**[[4o1y]] – pPLA2 + naphthalene acetic acid<br />
**[[3osh]] – NnPLA2G1+atropine


*Phospholipase A2  group II
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.


**[[1j1a]], [[3u8b]] – hPLA2G2A<br />
Atropine interacts with phospholipase 2A at residues asp29 and tyr49 on the protein. The
**[[1n28]], [[1n29]] – hPLA2G2A (mutant)<br />
<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.
**[[1cl5]], [[1fb2]], [[1vip]], [[2pvt]], [[2pyc]], [[5vet]] – DrPLA2 – ''Daboia russellii''<br />
**[[2qhw]] – DrPLA2 + gramine derivative<br />
**[[2que]] – DrPLA2 + ajamaline + anisic acid<br />
**[[1kqu]], [[1kvo]] – hPLA2G2A+substrate analog<br />
**[[3u8d]], [[3u8h]], [[3u8i]], [[4hmb]] - hPLA2G2A + inhibitor<br />
**[[5g3n]] - hPLA2G2A (mutant) + inhibitor<br />
**[[5wzw]], [[5wzv]], [[5wzu]], [[5wzt]], [[5wzs]], [[5wzo]], [[5wzm]] - hPLA2G2E + inhibitor<br />
**[[5yse]] - hPLA2G2E (mutant) + inhibitor<br />
**[[3g8f]] – DrPLA2G2+polypeptide<br />
**[[3mlm]] – PLA2G2 + myristic acid – ''Neuwiedi lancehead''<br />
**[[4fga]], [[4gfy]], [[4gld]] – DrPLA2 + polypeptide


*Human PLA2 group IVd
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.
**[[5iz5]] – hPLA2GIVd <br />
**[[5ixc]], [[5izr]] – hPLA2GIVd + fluorophosphonate derivative<br />


*Phospholipase A2 group V
== 3D Structures of Phospholipase A2 ==
[[Phospholipase A2 3D structures]]


**[[4rfp]] – PLA2 – chinese green tree viper
</StructureSection>
 
*Human phospholipase A2  group X
 
**[[1le6]], [[1le7]], [[4uy1]], [[5g3m]] – hPLA2G10<br />
**[[5owc]], [[5ow8]] - hPLA2G10 + inhibitor<br />
 
*Human phospholipase A2 group XV
 
**[[4x90]] – hPLA2G15<br />
**[[4x92]] – hPLA2G15 (mutant)<br />
**[[4x91]] – hPLA2G15 + IDFP<br />
**[[4x93]], [[4x94]], [[4x95]], [[4x97]] – hPLA2G15 + arachidonyl derivative<br />
 
*Human phospholipase A2  group XVI
 
**[[2kyt]], [[4dot]], [[4fa0]] – hPLA2G16 N-terminal<br />
 
*Phospholipase A2  group XIII
 
**[[4aup]] – PLA13 – whitish truffle
 
*Phospholipase A2 +inhibitor
 
**[[3o4m]], [[3hsw]] – PLA2+inhibitor <br />
**[[2azy]], [[2azz]], [[2b00]], [[2b01]], [[2b03]], [[2b04]]  – pPLA2+cholate derivative<br />
**[[1y6o]], [[1fx9]], [[1fxf]] – pPLA2+MJ33<br />
**[[1l8s]] – pPLA2+LPC-ether<br />
**[[5p2p]] – pPLA2+substrate analog<br />
**[[3nju]] – PLA2 group I+4-methoxy-benzoic acid – Andaman cobra<br />
**[[2wq5]] – PLA2+minocyclin – Indian cobra<br />
**[[1oxl]] – IcPLA2+indole<br />
**[[3h1x]], [[3fo7]] – IvPLA2+indomethacin <br />
**[[3fg5]] – IvPLA2+pentapeptide+ajmaline<br />
**[[3cbi]] – IvPLA2+anisic acid+ajmaline<br />
**[[2qu9]] – IvPLA2+eugenol<br />
**[[2otf]] – IvPLA2+atenolol<br />
**[[1zwp]] -  IvPLA2+nimesulide<br />
**[[1th6]] -  IvPLA2+atropine<br />
**[[1td7]] -  IvPLA2+niflumic acid<br />
**[[1tgm]] -  IvPLA2+aspirin<br />
**[[2wg9]] – rPLA2+octanoic acid<br />
**[[1oxr]] – NsPLA2+aspirin<br />
**[[1bk9]] – AhPLA2+PBPB<br />
**[[1fdk]] – bPLA2+MJ33<br />
**[[1mkv]] – bPLA2+transition state analog<br />
**[[1o2e]] – bPLA2 (mutant)+anisic acid<br />
**[[2b96]] - bPLA2+benzoic acid derivative<br />
**[[3bp2]] – bPLA2+pyruvic acid<br />
**[[1pob]] - NnPLA2+transition state analog<br />
**[[1poc]] - PLA2+transition state analog – Honey bee<br />
**[[1db4]], [[1db5]], [[1dcy]] – hPLA2+indole<br />
**[[1poe]] – hPLA2+phosphonyl inhibitor<br />
**[[1fv0]] – DrPLA2+aristolochic acid<br />
**[[1sv3]] - DrPLA2+benzoic acid derivative<br />
**[[1tp2]], [[2pws]], [[2q1p]] – DrPLA2+fatty acid<br />
**[[1sv9]], [[1sxk]], [[1zyx]], [[2b17]], [[2qvd]] – DrPLA2+anti-inflammatory agent<br />
**[[1kpm]] – DrPLA2+vitamin E<br />
**[[1oyf]] – DrPLA2+venom-6 methyl-heptanol<br />
**[[1q7a]] – DrPLA2+oxyphenabutazone<br />
**[[1y38]] – DrPLA2+glycerophosphate<br />
**[[1zr8]] – DrPLA2+ajmaline<br />
**[[2arm]] – DrPLA2+atropine<br />
**[[2dpz]] – DrPLA2 +hydroxyphenyl acetamide<br />
**[[2oli]], [[2oth]], [[2oyf]] – DrPLA2+indole derivative<br />
**[[2oub]] – DrPLA2+atenolol<br />
**[[4qem]] – DrPLA2 + coumaric acid<br />
**[[4qer]] – DrPLA2 + resveratrol<br />
**[[4qf7]] – DrPLA2 + corticosterone<br />
**[[4qf8]] – DrPLA2 + spermidine<br />
**[[4qgd]] – DrPLA2 + gramine derivative<br />
**[[4qmc]] – DrPLA2 + biotin derivative<br />
**[[2pmj]] – DrPLA2+benzopyrone<br />
**[[2zbh]] – DrPLA2+bavachalcone<br />
**[[4eix]] - DrPLA2+indomethacin + nimesulide<br />
**[[1po8]], [[1tc8]] – kPLA2+fatty acid<br />
**[[1xxs]] – PLA2+fatty acid – ''Bothrops moojeni''<br />
**[[2qhd]] – EcPLA2+fatty acid<br />
**[[3bjw]] – EcPLA2+suramin<br />
**[[1y4l]] – PLA2+suramin – ''Bothrops asper''
 
*Phospholipase A2 +polypeptide
 
**[[2o1n]], [[2d02]], [[2fnx]], [[1zm6]], [[1tdv]], [[1tg4]], [[1t37]] -  IvPLA2+polypeptide<br />
**[[1jq8]], [[1jq9]] - DsPLA2+polypeptide<br />
**[[1mf4]], [[2rd4]], [[3gci]], [[3jq5]], [[3jql]], [[3jti]] - NnPLA2+polypeptide<br />
**[[1skg]], [[1sqz]], [[1tg1]], [[1tj9]], [[1tjk]], [[1tk4]], [[2do2]], [[2g58]], [[2gns]], [[2pb8]] - DrPLA2+polypeptide
 
*Lp-PLA2
 
**[[1wab]] – bLP-PLA2 + acetate <br />
**[[1bwp]], 1bwq]], 1bwr]], 1es9]] – bLP-PLA2 ( mutant) <br />
**[[1fxw]] – bLP-PLA2 β + γ subunits<br />
**[[1uuj]] - mLP-PLA2 α subunit N terminal – mouse<br />
**[[1vyh]] - mLP-PLA2 α subunit C terminal + β subunit<br />
**[[3d59]] – hLP-PLA2 residues 47-429 <br />
*Lp-PLA2 binary complexes
**[[3dt6]] - bLP-PLA2 α subunit (mutant) + paraoxon<br />
**[[3dt8]] - bLP-PLA2 α subunit (mutant) + sarin<br />
**[[3dt9]] - bLP-PLA2 α subunit (mutant) + soman<br />
**[[3d5e]] - hLP-PLA2 residues 47-429 + paraoxon<br />
**[[3f96]] - hLP-PLA2 residues 47-429 + sarin<br />
**[[3f97]] - hLP-PLA2 residues 47-429 + soman<br />
**[[3f98]] - hLP-PLA2 residues 47-429 + tabun<br />
**[[3f9c]] - hLP-PLA2 residues 47-429 + DFP<br />
**[[5i8p]], [[5i9i]], [[5jad]], [[5jah]], [[5jal]], [[5jan]], [[5jao]], [[5jap]], [[5jar]], [[5jas]], [[5jat]], [[5jau]], [[5lp1]], [[5lz2]], [[5lz8]], [[5lz9]] - hLP-PLA2 residues 47-429 + inhibitor<br />
**[[5lyy]], [[5lz4]], [[5lz5]], [[5lz7]] - hLP-PLA2 residues 47-429 (mutant) + inhibitor<br />
 
*Bothrops toxins
 
**[[3i3h]], [[3i3i]], [[3hzd]], [[2oqd]], [[1zlb]], [[1umv]], [[1u73]], [[1zl7]]  – BTX<br />
**[[3jr8]] – BTXD+Ca<br />
**[[3hzw]], [[3i03]] – BTX+BPB<br />
**[[3iq3]], [[2h8i]] – BTX + PEG<br />
**[[1z76]] – BTX+bromophenacyl<br />
**[[1gmz]], [[1qll]], [[2q2j]], [[2ok9]]  - PTX<br />
**[[3cyl]], [[3cxi]] – PTX+a-tocopherol<br />
**[[2oqd]], [[3jr8]] – BTX-II<br />
 
*Viperotoxin
 
**[[1oqs]] – DrRV4/RV7
 
*cPhospholipase A2
 
**[[1cjy]] - h-cPLA2<br />
**[[1bci]] – h-cPLA2 C2 domain
 
*Pro-Phospholipase A2


**[[1hn4]] – pPPLA2+MJ33<br />
**[[4bp2]] – bPPLA2
}}
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

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