Phospholipase A2

From Proteopedia

Revision as of 06:52, 29 June 2016

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 Contents 1 Function 2 Relevance 3 Crystal structure of porcine pancreatic phospholipase A2 in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione Function Phospholipase A2 (PLA2) is an enzyme which releases fatty acids from glycerol. It is found in mammals and in snake venoms[1]. 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[2]. PLA2 group V is active in leukocytes recruitment[3]. PLA2 group X regulates cysteinyl leukotriene synthesis[4]. PLA2 group XV is located in the endocytic system and may be involved in CD1d function[5]. PLA2 group XVI is adipose-specific[6]. 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 complex see Diclofenac binding to Phospholipase A2. 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[7]. Crystal structure of porcine pancreatic phospholipase A2 in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione [8] 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.

3D Structures of Phospholipase A2

Updated on 29-June-2016 {{#tree:id=OrganizedByTopic|openlevels=0|

• 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, 3l69, 3tt5, 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 – DrPLA2 – Daboia russellii
    
  • 2qhw – DrPLA2 + gramine derivative
    
  • 2que – DrPLA2 + ajamaline + anisic acid
    
  • 1kqu, 1kvo – hPLA2G2A+substrate analog
    
  • 3u8d, 3u8h, 3u8i, 4hmb - hPLA2G2A + inhibitor
    
  • 3g8f – DrPLA2G2+polypeptide
    
  • 3mlm – PLA2G2 + myristic acid – Neuwiedi lancehead
    
  • 4fga, 4gfy, 4gld – DrPLA2 + polypeptide

• Phospholipase A2 group V

• • 4h0q, 4rfp – PLA2 – chinese green tree viper

• Human phospholipase A2 group X

• • 1le6, 1le7, 4uy1 – hPLA2G10

• 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 – bovine
    
  • 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 – human
    

• 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 - hLP-PLA2 residues 47-429 + 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

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References

1. ↑ Dennis EA. Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem. 1994 May 6;269(18):13057-60. PMID:8175726
2. ↑ Leitinger N, Watson AD, Hama SY, Ivandic B, Qiao JH, Huber J, Faull KF, Grass DS, Navab M, Fogelman AM, de Beer FC, Lusis AJ, Berliner JA. Role of group II secretory phospholipase A2 in atherosclerosis: 2. Potential involvement of biologically active oxidized phospholipids. Arterioscler Thromb Vasc Biol. 1999 May;19(5):1291-8. PMID:10323782
3. ↑ Lapointe S, Brkovic A, Cloutier I, Tanguay JF, Arm JP, Sirois MG. Group V secreted phospholipase A2 contributes to LPS-induced leukocyte recruitment. J Cell Physiol. 2010 Jul;224(1):127-34. doi: 10.1002/jcp.22106. PMID:20232296 doi:http://dx.doi.org/10.1002/jcp.22106
4. ↑ Hallstrand TS, Lai Y, Hooper KA, Oslund RC, Altemeier WA, Matute-Bello G, Gelb MH. Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils. J Allergy Clin Immunol. 2016 Jan;137(1):268-77.e8. doi:, 10.1016/j.jaci.2015.05.026. Epub 2015 Jun 30. PMID:26139511 doi:http://dx.doi.org/10.1016/j.jaci.2015.05.026
5. ↑ Platt RW, Brookhart MA, Cole SR, Westreich D, Schisterman EF. Reply to taguri and matsuyama. Stat Med. 2013 Sep 10;32(20):3592-3. doi: 10.1002/sim.5805. PMID:23943550 doi:http://dx.doi.org/10.1002/sim.5805
6. ↑ Duncan RE, Sarkadi-Nagy E, Jaworski K, Ahmadian M, Sul HS. Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA). J Biol Chem. 2008 Sep 12;283(37):25428-36. doi: 10.1074/jbc.M804146200. Epub 2008, Jul 9. PMID:18614531 doi:http://dx.doi.org/10.1074/jbc.M804146200
7. ↑ Quach ND, Arnold RD, Cummings BS. Secretory phospholipase A2 enzymes as pharmacological targets for treatment of disease. Biochem Pharmacol. 2014 Aug 15;90(4):338-48. doi: 10.1016/j.bcp.2014.05.022. Epub, 2014 Jun 4. PMID:24907600 doi:http://dx.doi.org/10.1016/j.bcp.2014.05.022
8. ↑ Crystal structure of porcine pancreatic phospholipase a2 in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione. Dileep KV, Tintu I, Mandal PK, Karthe P, Haridas M, Sadasivan C. Frontiers In Life Sci. (2012) doi:http://dx.doi.org/10.1080/21553769.2012.689262