Phospholipase A2

Function Phospholipase A2 (PLA2) is an enzyme which releases fatty acids from glycerol. It is found in mammals and in snake venoms. PLA2 releases arachidonic acid from membranes causing inflammation and pain. The PLA2 contains many isozymes which are ordered by groups and named accordingly, ie., group I is PLA2G1. PLA2 group II is induced in inflammation and present in atherosclerotic lesions. PLA2 group V is active in leukocytes recruitment. PLA2 group X regulates cysteinyl leukotriene synthesis. PLA2 group XV is located in the endocytic system and may be involved in CD1d function. PLA2 group XVI is adipose-specific. Lipoprotein-associated phospholipase A2 or platelet-activating factor acetylhydrolase (Lp-PLA2) degrades platelet-activating factor and oxidized phospholipids into inactive metabolites. Platelet-activating factor is a potent phospholipid activator and mediator of inflammation, platelet aggregation and other leukocyte functions. . Bothropstoxin (BTX) is PLA2 from the snake Bothrops jararacussu. Piratoxin (PTX) is PLA2 from the snake Bothrops piraña. Viperotoxin (VTX) is a heterodimer of a very homologous PLA2 called RV-4/RV-7. Cystolic PLA2 (cPLA2) is intracellular. It is larger than the secreted PLA2 and contains the targeting C2 domain. Pro-phosphlipase (PPLA2) is a pancreatic PLA2 whose 7-mer N-terminal peptide is cleaved off to produce the active PLA2. For details on Lys49 snake-venom PLA2 see Anum-II. For PLA2 inhibitor see Atropine See also Phospholipase (Hebrew). Relevance PLA2 serve as pharmacological targets for therapeutical treatment of diseases like atherosclerosis, immune disorders, cardiovascular diseases and cancer. 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. Diclofenac binding to Phospholipase A2 Abstract from Pubmed Type IIA secretory phospholipase A2 (PLA2) enzymes catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids to release fatty acids and lysophospholipids. In order to elucidate the role of PLA2 in inflammatory disorders and to determine the mode of binding of non-steroidal anti-inflammatory drugs (NSAIDs) to PLA2, the detailed three-dimensional structure of a complex formed between a group IIA PLA2 from Daboia russelli pulchella and 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid (diclofenac) has been determined. The preformed complex was crystallized by equilibrating the protein solution against a mixture of 0.20 M ammonium sulfate and 30% PEG 4000. The crystals belong to space group P4(3), with unit-cell parameters a = b = 53.0, c = 48.4 A. The structure was solved by the molecular-replacement method and refined to R(cryst) and R(free) factors of 0.192 and 0.211, respectively, using reflections to 2.7 A resolution. The structure showed that diclofenac occupies a very favourable position in the centre of the substrate-binding hydrophobic channel that allows a number of intermolecular interactions. The binding mode of diclofenac involved crucial interactions with important residues for substrate recognition such as Asp49, His48 and Gly30. In addition, it included three new interactions involving its Cl atoms with Phe5, Ala18 and Tyr22. It also showed an extensive network of hydrophobic interactions involving almost all of the residues of the substrate-binding hydrophobic channel. The binding affinity of diclofenac was determined using surface plasmon resonance, which gave an equilibrium constant of 4.8 +/- 0.2 x 10(-8) M. The shows three mail helices in phospholipase A2. The are His 48, Asp 49, Tyr 52 and Glu 99 in the structure. Diclofenac makes several with the substrate binding site of enzyme. ligand binding is shown in model of the complex. Crystal structure of porcine pancreatic phospholipase A2 in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione possesses anti-inflammatory activity. The binding of curcumin with PLA2 was studied using X-ray crystallography. Since the electron density found in the active site did not match with curcumin, (the photo-degraded product of curcumin) in the unexplained electron density. To understand the , molecular docking studies was carried out. with respect to the ligand position and identified that of PLA2 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 PLA2.

spinqualitylabelsall models Phospholipase A2 complex with ethanol, phosphate and Ca+2 ion (green) (PDB code 1yxh) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of Phospholipase A23D Structures of Phospholipase A2

Updated on 13-November-2019

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• Phospholipase A2
  • 1une, 1mkt, 1irb, 1bp2, 1bpq, 1g4i, 2bp2, 2bpp - bPLA2 – bovine
    
  • 2zp3, 2zp4, 2zp5, 1c74, 1kvw, 1kvx, 1kvy, 1ceh, 1mks, 1mku, 1vkq, 1vl9, 2bax, 2bch, 2bd1, 1o3w, 1gh4 – bPLA2 (mutant) – bovine
    
  • 1bvm – bPLA2 - NMR
    
  • 1qll, 2q2j – PLA2 – Bothrops pirajai
    
  • 2qog – PLA2 – Crotalus durissus
    
  • 2ph4 – PLA2 – Zhaoermia mangshanensis
    
  • 2h4c, 1q6v – IvPLA2 – Indian viper
    
  • 1vpi – PLA2 – sand viper
    
  • 2osn, 1fe5, 1dpy – kPLA2 – krait
    
  • 1g0z, 1g2x – kPLA2 (mutant)
    
  • 2wg7, 2wg8 – rPLA2 – rice
    
  • 1p2p, 4p2p – pPLA2 - pig
    
  • 1y6p, 2phi, 3p2p – pPLA2 (mutant) – pig
    
  • 1sfv, 1sfw, 1pir, 1pis – pPLA2 - NMR
    
  • 1yxh – NsPLA2 – Naja sagittifera
    
  • 1oz6, 2qhe – PLA2 – Echis carinatus
    
  • 1it4, 1it5 – PLA2 – Stretomyces violaceoruber – NMR
    
  • 1mg6 – PLA2 – Agkistrodon acutus
    
  • 1s8g, 1s8h, 1s8i – PLA2 – copperhead
    
  • 1ijl – PLA2 – Deinagkistrodon acutus
    
  • 1mc2, 4hg9 – PLA2 – Chinese moccasin
    
  • 1c74, 1kvw, 1kvx, 1kvy, 1ceh – bPLA2 (mutant) – bovine
    
  • 1b4w, 1jia, 1c1j – AhPLA2 - Agkistrodon halys
    
  • 1a2a, 1m8r, 1m8s, 1psj – PLA2 – Gloydius halys
    
  • 1a3d, 1a3f, 1ln8, 1mh2, 1mh8, 1ows, 1poa, 1psh, 1s6b, 1sz8, 1xxw, 1y75, 1yxl, 1yxh – PLA2 – Naja naja
    
  • 1mh7 - PLA2 – Naja sagittifera
    
  • 2osh – PLA2 – Chinese cobra
    
  • 1ae7, 2not, 4e4c – PLA2 – Notechis scutatus
    
  • 1aok, 1jlt, 1q5t, 1rgb, 3dih, 3g8g, 3g8h – PLA2 – Vipera ammodytes
    
  • 2i0u – PLA2 – Vipera nikolskii
    
  • 1ayp, 1bbc, 1pod – hPLA2 – human
    
  • 1rlw – hPLA2 CALB domain
    
  • 1faz, 1kp4 – PLA2 – Streptomyces violaceruber
    
  • 1god – PLA2 – Cerrophidion godmani
    
  • 1gp7, 1m8t – PLA2 – Ophiophagus hanna
    
  • 1ozy, 1p7o, 1pwo – PLA2 – Micropechis ikahena
    
  • 1pp2 – PLA2 – rattlesnake
    
  • 1ppa, 1vap – PLA2 – cottonmouth
    
  • 1u4j – PLA2 – Bungarus caeruleus
    
  • 2aoz – PLA2 – Atropoides nummifer
    
  • 3v9m – PLA2 – king brown snake
    
• Phospholipase A2 group I
  • 3elo – hPLA2G1B
    
  • 3q4y - PLA2G1 - Andaman cobra
    
  • 3fvi, 3fvj – pPLA2G1B+octyl sulfate
    
  • 3qlm - pPLA2G1B + hexadecanoic acid
    
  • 3l30, 4dbk - pPLA2G1B+berberine derivative
    
  • 4g5i – pPLA2 + DBP
    
  • 4o1y – pPLA2 + naphthalene acetic acid
    
  • 3osh – NnPLA2G1+atropine
• Phospholipase A2 group II
  • 1j1a, 3u8b – hPLA2G2A
    
  • 1n28, 1n29 – hPLA2G2A (mutant)
    
  • 1cl5, 1fb2, 1vip, 2pvt, 2pyc, 5vet – DrPLA2 – Daboia russellii
    
  • 2qhw – DrPLA2 + gramine derivative
    
  • 2que – DrPLA2 + ajamaline + anisic acid
    
  • 1kqu, 1kvo – hPLA2G2A+substrate analog
    
  • 3u8d, 3u8h, 3u8i, 4hmb - hPLA2G2A + inhibitor
    
  • 5g3n - hPLA2G2A (mutant) + inhibitor
    
  • 5wzw, 5wzv, 5wzu, 5wzt, 5wzs, 5wzo, 5wzm - hPLA2G2E + inhibitor
    
  • 5yse - hPLA2G2E (mutant) + inhibitor
    
  • 3g8f – DrPLA2G2+polypeptide
    
  • 3mlm – PLA2G2 + myristic acid – Neuwiedi lancehead
    
  • 4fga, 4gfy, 4gld – DrPLA2 + polypeptide
• Human PLA2 group IVd

• • 5iz5 – hPLA2GIVd
    
  • 5ixc, 5izr – hPLA2GIVd + fluorophosphonate derivative
    
• Phospholipase A2 group V
  • 4rfp – PLA2 – chinese green tree viper
• Human phospholipase A2 group X
  • 1le6, 1le7, 4uy1, 5g3m – hPLA2G10
    
  • 5owc, 5ow8 - hPLA2G10 + inhibitor
    
• Human phospholipase A2 group XV
  • 4x90 – hPLA2G15
    
  • 4x92 – hPLA2G15 (mutant)
    
  • 4x91 – hPLA2G15 + IDFP
    
  • 4x93, 4x94, 4x95, 4x97 – hPLA2G15 + arachidonyl derivative
    
• Human phospholipase A2 group XVI
  • 2kyt, 4dot, 4fa0 – hPLA2G16 N-terminal
    
• Phospholipase A2 group XIII
  • 4aup – PLA13 – whitish truffle
• Phospholipase A2 +inhibitor
  • 3o4m, 3hsw – PLA2+inhibitor
    
  • 2azy, 2azz, 2b00, 2b01, 2b03, 2b04 – pPLA2+cholate derivative
    
  • 1y6o, 1fx9, 1fxf – pPLA2+MJ33
    
  • 1l8s – pPLA2+LPC-ether
    
  • 5p2p – pPLA2+substrate analog
    
  • 3nju – PLA2 group I+4-methoxy-benzoic acid – Andaman cobra
    
  • 2wq5 – PLA2+minocyclin – Indian cobra
    
  • 1oxl – IcPLA2+indole
    
  • 3h1x, 3fo7 – IvPLA2+indomethacin
    
  • 3fg5 – IvPLA2+pentapeptide+ajmaline
    
  • 3cbi – IvPLA2+anisic acid+ajmaline
    
  • 2qu9 – IvPLA2+eugenol
    
  • 2otf – IvPLA2+atenolol
    
  • 1zwp - IvPLA2+nimesulide
    
  • 1th6 - IvPLA2+atropine
    
  • 1td7 - IvPLA2+niflumic acid
    
  • 1tgm - IvPLA2+aspirin
    
  • 2wg9 – rPLA2+octanoic acid
    
  • 1oxr – NsPLA2+aspirin
    
  • 1bk9 – AhPLA2+PBPB
    
  • 1fdk – bPLA2+MJ33
    
  • 1mkv – bPLA2+transition state analog
    
  • 1o2e – bPLA2 (mutant)+anisic acid
    
  • 2b96 - bPLA2+benzoic acid derivative
    
  • 3bp2 – bPLA2+pyruvic acid
    
  • 1pob - NnPLA2+transition state analog
    
  • 1poc - PLA2+transition state analog – Honey bee
    
  • 1db4, 1db5, 1dcy – hPLA2+indole
    
  • 1poe – hPLA2+phosphonyl inhibitor
    
  • 1fv0 – DrPLA2+aristolochic acid
    
  • 1sv3 - DrPLA2+benzoic acid derivative
    
  • 1tp2, 2pws, 2q1p – DrPLA2+fatty acid
    
  • 1sv9, 1sxk, 1zyx, 2b17, 2qvd – DrPLA2+anti-inflammatory agent
    
  • 1kpm – DrPLA2+vitamin E
    
  • 1oyf – DrPLA2+venom-6 methyl-heptanol
    
  • 1q7a – DrPLA2+oxyphenabutazone
    
  • 1y38 – DrPLA2+glycerophosphate
    
  • 1zr8 – DrPLA2+ajmaline
    
  • 2arm – DrPLA2+atropine
    
  • 2dpz – DrPLA2 +hydroxyphenyl acetamide
    
  • 2oli, 2oth, 2oyf – DrPLA2+indole derivative
    
  • 2oub – DrPLA2+atenolol
    
  • 4qem – DrPLA2 + coumaric acid
    
  • 4qer – DrPLA2 + resveratrol
    
  • 4qf7 – DrPLA2 + corticosterone
    
  • 4qf8 – DrPLA2 + spermidine
    
  • 4qgd – DrPLA2 + gramine derivative
    
  • 4qmc – DrPLA2 + biotin derivative
    
  • 2pmj – DrPLA2+benzopyrone
    
  • 2zbh – DrPLA2+bavachalcone
    
  • 4eix - DrPLA2+indomethacin + nimesulide
    
  • 1po8, 1tc8 – kPLA2+fatty acid
    
  • 1xxs – PLA2+fatty acid – Bothrops moojeni
    
  • 2qhd – EcPLA2+fatty acid
    
  • 3bjw – EcPLA2+suramin
    
  • 1y4l – PLA2+suramin – Bothrops asper
• Phospholipase A2 +polypeptide
  • 2o1n, 2d02, 2fnx, 1zm6, 1tdv, 1tg4, 1t37 - IvPLA2+polypeptide
    
  • 1jq8, 1jq9 - DsPLA2+polypeptide
    
  • 1mf4, 2rd4, 3gci, 3jq5, 3jql, 3jti - NnPLA2+polypeptide
    
  • 1skg, 1sqz, 1tg1, 1tj9, 1tjk, 1tk4, 2do2, 2g58, 2gns, 2pb8 - DrPLA2+polypeptide
• Lp-PLA2
  • 1wab – bLP-PLA2 + acetate
    
  • 1bwp, 1bwq]], 1bwr]], 1es9]] – bLP-PLA2 ( mutant)
    
  • 1fxw – bLP-PLA2 β + γ subunits
    
  • 1uuj - mLP-PLA2 α subunit N terminal – mouse
    
  • 1vyh - mLP-PLA2 α subunit C terminal + β subunit
    
  • 3d59 – hLP-PLA2 residues 47-429
    

• Lp-PLA2 binary complexes

• • 3dt6 - bLP-PLA2 α subunit (mutant) + paraoxon
    
  • 3dt8 - bLP-PLA2 α subunit (mutant) + sarin
    
  • 3dt9 - bLP-PLA2 α subunit (mutant) + soman
    
  • 3d5e - hLP-PLA2 residues 47-429 + paraoxon
    
  • 3f96 - hLP-PLA2 residues 47-429 + sarin
    
  • 3f97 - hLP-PLA2 residues 47-429 + soman
    
  • 3f98 - hLP-PLA2 residues 47-429 + tabun
    
  • 3f9c - hLP-PLA2 residues 47-429 + DFP
    
  • 5i8p, 5i9i, 5jad, 5jah, 5jal, 5jan, 5jao, 5jap, 5jar, 5jas, 5jat, 5jau, 5lp1, 5lz2, 5lz8, 5lz9 - hLP-PLA2 residues 47-429 + inhibitor
    
  • 5lyy, 5lz4, 5lz5, 5lz7 - hLP-PLA2 residues 47-429 (mutant) + inhibitor
    
• Bothrops toxins
  • 3i3h, 3i3i, 3hzd, 2oqd, 1zlb, 1umv, 1u73, 1zl7 – BTX
    
  • 3jr8 – BTXD+Ca
    
  • 3hzw, 3i03 – BTX+BPB
    
  • 3iq3, 2h8i – BTX + PEG
    
  • 1z76 – BTX+bromophenacyl
    
  • 1gmz, 1qll, 2q2j, 2ok9 - PTX
    
  • 3cyl, 3cxi – PTX+a-tocopherol
    
  • 2oqd, 3jr8 – BTX-II
    
• Viperotoxin
  • 1oqs – DrRV4/RV7
• cPhospholipase A2
  • 1cjy - h-cPLA2
    
  • 1bci – h-cPLA2 C2 domain
• Pro-Phospholipase A2
  • 1hn4 – pPPLA2+MJ33
    
  • 4bp2 – bPPLA2