Phospholipase A2: Difference between revisions

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== References ==
== References ==
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[[Category:Topic Page]]

Revision as of 01:45, 22 October 2017

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[7].
    .
  • 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[8]. 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[9].

Crystal structure of porcine pancreatic phospholipase A2 in complex with 2-methoxycyclohexa-2-5-diene-1,4-dione

[10]

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.

Phospholipase A2 complex with ethanol, phosphate and Ca+2 ion (green) (PDB code 1yxh)

Drag the structure with the mouse to rotate

3D Structures of Phospholipase A23D Structures of Phospholipase A2

Updated on 22-October-2017

    • 5ixc – hPLA2GIVD + fluorophosphonate derivative
  • Phospholipase A2 group V
    • 4rfp – PLA2 – chinese green tree viper
  • Human phospholipase A2 group X
  • Human phospholipase A2 group XV
  • Human phospholipase A2 group XVI
  • 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
  • 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

ReferencesReferences

  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. Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA, Yamada Y, McIntyre TM, Prescott SM, Gray PW. Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature. 1995 Apr 6;374(6522):549-53. PMID:7700381 doi:http://dx.doi.org/10.1038/374549a0
  8. 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
  9. Tellis CC, Tselepis AD. The role of lipoprotein-associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. Biochim Biophys Acta. 2009 May;1791(5):327-38. doi: 10.1016/j.bbalip.2009.02.015. PMID:19272461 doi:http://dx.doi.org/10.1016/j.bbalip.2009.02.015
  10. 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

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