Jia, Ying

Olvera, Pablo

English

Scholarworks@UTRGV Univ. of Texas RioGrande Valley

University of Texas Rio Grande Valley ScholarWorks @ UTRGV Biology Faculty Publications and Presentations College of Sciences 7-23-2018 Snake Venom Phospholipase A2 And Its Antibacterial Potential Pablo Olvera Ying Jia Follow this and additional works at: https://scholarworks.utrgv.edu/bio_fac  Part of the Biology Commons Snake Venom Phospholipase A2 and Its Antibacterial PotentialPablo Olvera and Ying Jia*Biology Department, College of Sciences, The University of Texas Rio Grande Valley, Brownsville, TX 78520, USA*Corresponding author: Ying Jia, Biology Department, College of Sciences, The University of Texas Rio Grande Valley, Brownsville, TX 78520,USA, Tel: 956-882-7320; E-mail: ying.jia@utrgv.eduReceived date: July 15, 2018; Accepted date: July 18, 2018; Published date: July 23, 2018Citation: Olvera P, Jia Y (2018) Snake Venom Phospholipase A2 and Its Antibacterial Potential. J Mol Sci. Vol. 2 No. 2: 9.Copyright: © 2018 Olvera P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Snake Venom Phospholipase A2Phospholipases are a class of ubiquitous enzymes that havethe common substrate, phospholipid, and they all hydrolyzethe different ester linkages of phospholipid. Depending onwhich ester linkage hydrolyzed, phospholipases are groupedinto four major categories-A, B, C and D. Phospholipase A,originally termed as lecithinase A by Contardi and Ercoli [1],was found for the first time in the venoms of cobra viperfamily at the end of 19th century, and was further divided intoPhospholipase A1 (cleaves the sn-1 acyl ester of the glycerolbackbone) and phospholipase A2 (cleaves the sn-2 acyl ester ofthe glycerol backbone). Phospholipase B cleaves either sn-1 orsn-2 acyl ester of the glycerol backbone. Both phospholipase Aand B enzyme are also known as a lysophospholipase.Phospholipase C and D are the phosphodiesterases, and theycleave before and after the phosphate, respectively [2]. Snakevenom phospholipase hydrolyze the 2-acyl groups in sn-3-phosphoglycerides, thus belong to phospholipase A2 (PLA2). In1994, Dennis for the first time established the systematicgroup numbering system for PLA2 enzymes; afterwards, PLA2family has grown continuously, and now the superfamily ofPLA2 enzymes currently consists of 16 Groups [3] [4,5]. Themajor five types of PLA2s in this 16 groups are Ca+2-dependentsecretory PLA2s (sPLA2), Ca+2-dependent cytosolic PLA2s(cPLA2), Ca2+-independent intracellular PLA2s (iPLA2), plateletactivation factor acetyl hydrolases (PAF-AH), and lysosomalPLA2s [6]. Snake venom PLA2s, part of secretory PLA2 (sPLA2),from old world snakes (Elapidae family) including Kraits(Bungarus species), the Indian cobra species (Naja species),tiger snake (Hemachatus haemuchatus) and the Australiantiger snake (Notechis scututus scutatus) belong to group IA,while from new world snakes (Crotalidae family) includingJapanese water moccasin, rattlesnakes and vipers belong togroup IIA, as well as from Viperidae family including Gaboonadder, Bitis gabonica belong to IIB [7,8]. Compared with GroupI snake venom PLA2s, the most distinguishing characteristic ofGroup II snake venom PLA2 enzymes is the presence of anegative charged COOH-terminal extension of 6-7 residues [7].Based on the amino acid composition surrounding the activesite, Group II snake venom PLA2s can be divided into, at least,two isoforms: (a) the Asp49 enzymes, having an aspartic acidresidue at position 49, show catalytic activity, and (b) theLys49 proteins, possessing a lysine residue at position 49, arecatalytically inactive [9]. According to the primary structureand pI, the catalytically-active isoforms can be furthersubdivided into acidic and basic sub-isoforms, and thecatalytically-inactive isoforms (Lys49) into only basic sub-isoforms [10]. In addition, two S49 PLA2 (Serine residue atposition 49) proteins [11,12], and one R49 PLA2 (Arginineresidue at positon 49) from snake (Protobothropsmucrosquamatus) [13] have been reported, suggesting theexistence of more PLA2 isoforms in the snake venoms.Proteins and peptides (commonly referred to as toxins)constitute 90-95% of the dry weight of snake venom, andbelong to relatively small stable protein families [14,15]. PLA2sare the major component of snake venom proteomes,especially in the venoms of Agkistrodon contortrix contortrix[16], Micrurus lemniscatus [17], Agkistrodon piscivorusleucostoma [18-20], and Bungarus multicinctus [14]. Due tothe pharmacological and physiopathological effects of snakevenom PLA2 in living organisms, snake venom PLA2s have beenextensively studied. Since two proteins with phospholipase Aactivity were purified from venom of Eastern diamondbackrattlesnake (Crotus. adamanteus) [21] and crystalized [22], andone phospholipase A2 with MW of 14.5 purified from thevenom of snake (Crotalus atrox) [23], more than 500 PLA2sisolated from snake venoms (based on NCBI and UniProtdatabases). The amino acid sequences of many snake venomPLA2s have already determined, and some of their structureshave been resolved by X-ray crystallography. The secretedPLA2s including snake venom PLA2s are characterized by a lowmolecular weight (13-15 kDa), and containing histidine in thecatalytic site, Ca2+ bond in the active site, six conserveddisulfide bonds with one or two variable disulfide bonds [24],and more than 50% α-helix and 10% β-sheet [25].Antibacterial Potential of SnakeVenom PLA2Snake venoms contain numerous medically importantproteins and peptides with varied physiological activities[26,27]. Since Glaser [28] experimentally observed, for the firsttime, the bactericidal activity of venom from Crotalus snakes, aconsiderable body of work has been reported the antibacterialeffects of the crude venoms as well as venom componentsEditorialiMedPub Journalswww.imedpub.comJournal of Molecular SciencesVol.2 No.2:92018© Copyright iMedPub | This article is available from: http://www.imedpub.com/journal-molecular-sciences/archive.php 1from different snake species. The major components reportedpossessing antibacterial activity in snake venom to dateinclude PLA2 [29], L-amino acid oxidase [30],metalloproteinase [31] and lectin [32]. Among these venommolecules, PLA2 is well documented possessing antibacterialactivity. Forst et al. [33] demonstrated that PLA2s from thevenoms of snakes (Agkistrodon halys blomhoffii) and(Agkistrodon halys palas) actively hydrolyzed thephospholipids of the bactericidal/permeability-increasingprotein (BPI)-treated E. coli. Since then, many researchersclaimed that snake venom PLA2s exert antibacterial effects[13,29,34-46]. However, it is interesting that Resende et al.[47] and Jia et al. [48] reported that PLA2s isolated fromcottonmouth snake venoms display no antibacterial effects,implying that not all snake venom PLA2 possesses antibacterialeffects. The precise bactericidal mechanisms of Group IIA PLA2such as hnpsPLA2 isolated from human tissues and cells wereclarified, and the authors demonstrated that the antibacterialactivity of hnpsPLA2 is due to a large excess of cationicresidues on its surface [49]. However, it seems that themolecular mechanisms underpinning antibacterial activity ofsnake venom PLA2 are varied [29,39,41] or need to bedetermined.References1. Contardi A, Ercoli A (1932) Uber die enzymatische spaltung derlecithine and lysocithine. Biochem 261: 275.2. Waite M (1987) Phospholipases. In: Donald J Hanahan (Ed),Handbook of Lipid Research. Plenum Press, New York, NY.3. Dennis EA (1994) Diversity of group types, regulation, andfunction of phospholipase A2. J Biol Chem 269: 13057-13060.4. Schaloske RH, Dennis EA (2006) The phospholipase A2superfamily and its group numbering system. Biochimica etBiophysica Acta (BBA) - Molecular and Cell Biology of Lipids1761: 1246-1259.5. Duncan RE, Sarkadi-Nagy E, Jaworski K, Ahmadian M, Sul HS(2008) Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA). J Biol Chem 283:25428-25436.6. Dennis EA, Cao J, Hsu YH, Magrioti V, Kokotos G (2011)Phospholipase A2 enzymes: Physical structure, biologicalfunction, disease implication, chemical inhibition, andtherapeutic intervention. Chem Rev 111: 6130-6185.7. Heinrikson RL, Krueger ET, Keim PS (1977) Amino acid sequenceof phospholipase A2-α from the venom of Crotalus adamanteus.J Biol Chem 252: 4913-4921.8. Davidson FF, Dennis EA (1990) Evolutionary relationships andimplications for the regulation of phospholipase A2 from snakevenom to human secreted forms. J Mol Evol 31: 228-238.9. Maraganore JM, Merutka G, Cho W, Welches W, Kezdy FJ, et al.(1984) A new class of phospholipases A2 with lysine in place ofaspartate 49. Functional consequences for calcium andsubstrate binding. J Biol Chem 259: 13839-13843.10. Lomonte B, Rangel J (2012) Snake venom Lys49 myotoxins: Fromphospholipases A2 to non-enzymatic membrane disruptors.Toxicon 60: 520-530.11. Krizaj I, Bieber AL, Ritonja A, Gubensek F (1991) The primarystructure of ammodytin L, a myo- toxic phospholipase A2homologue from Vipera ammodytes venom. Eur J Biochem 202:1165-1168.12. Polgar J, Magnenat EM, Peitsch MC, Wells TNC, Clemetson KJ(1996) Asp-49 is not an absolute prerequisite for the enzymicactivity of low-Mr phospholipases A2: purification,characterization and computer modelling of an enzymicallyactive Ser-49 phospholipase A2, ecarpholin S, from the venomof Echis carinatus sochureki (saw-scaled viper). Biochem J 319:961-968.13. Wei JF, Li T, Wei XL, Sun QY, Yang FM, et al. (2006) Purification,characterization and cytokine release function of a novel Arg-49phospholipase A2 from the venom of Protobothropsmucrosquamatus. Biochimie 88: 1331-1342.14. Tu AT (1988) Snake venoms: general background andcomposition. In: Venoms: Chemistry and Molecular Biology.John Willey and Sons, New York pp: 1-19.15. Fry BG, Wuster W (2004) Assembling an arsenal: origin andevolution of the snake venom proteome inferred fromphylogenetic analysis of toxin sequences. Mol Biol Evol 21:870-873.16. Bocian A, Urbanik M, Hus K, Lyskowski A, Petrilla V, et al. (2016)Proteomic analyses of Agkistrodon contortrix contortrix venomusing 2D electrophoresis and MS technique. Toxins 8: 372.17. Casais-e-Silva LL, Teixeira CFP, Lebrun I, Lomonte B, Gutiérrez JM(2016) Leminitoxin, the major component of Micrurusleminiscatus coral snake venom is a myotoxic and pro-inflammatory phospholipase A2. Toxicol Lett 257: 60-71.18. Lomonte B, Tsai WC, Ureña-Diaz JM, Sanz L, Mora-Obando D, etal. (2014) Venomics of New world pit vipers: genus-widecomparisons of venom proteomes across Agkistrodon. JProteomics 96: 103-116.19. Jia Y, Cantu BA, Sanchez EE, Perez JC (2008) ComplementaryDNA sequencing and identification of mRNAs from venomousgland of Agkistrodon piscivorus leucostoma. Toxicon 51:1457-1466.20. Jia Y, Ermolinsky B, Garza A, Provenzano D (2017) PhospholipaseA2 in the venom of three cottonmouth snakes. Toxicon 135:84-92.21. Saito K, Hanahan DJ (1962) A study of the purification andproperties of the phospholipase A of Crotalus adamanteusvenom. Biochemistry 1: 521-532.22. Wells MA, Hanahan DJ (1969) Phospholipase A. I. Isolation andcharacterization of two enzymes from Crotalus adamanteusvenom. Biochemistry 8: 414-424.23. Wu TW, Tinker DO (1969) Phospholipase A2 from Crotalus atroxvenom. I. Purification and some properties. Biochemistry 8:1558-1568.24. Burke JE, Dennis EA (2009) Phospholipase A2 structure⁄function,mechanism, and signaling. J Lipid Res 50: S237-S242.25. Dufton MJ, Eaker D, Hider RC (1983) Conformational propertiesof phospholipase A2 -secondary structure predication, circulardichroism and relative interface hydrophobicity. Eur J Biochem137: 537-544.26. Calvete JJ, Fasoli E, Sanz L, Boschetti E, Righetti PG (2009)Exploring the Venom Proteome of the Western DiamondbackRattlesnake, Crotalus atrox, via Snake Venomics andJournal of Molecular SciencesVol.2 No.2:920182 This article is available from: http://www.imedpub.com/journal-molecular-sciences/archive.phpCombinatorial Peptide Ligand Library Approaches. J ProteomeResearch 8: 3055-3067.27. Casewell NR, Wagstaff SC, Wűster W, Cook DAN, Bolton FMS, etal. (2014) Medically important differences in snake venomcomposition are dictated by distinct postgenomic mechanisms.PNAS 111: 9205-9210.28. Glasser HR (1948) Bactericidal activity of Crotalus venom invitro. Copeia 4: 245-247.29. Páramo L, Lomonte B, Pizarro-Cerdá J, Bengoechea JA, Gorvel JP,et al. (1998) Bactericidal activity of Lys49 and Asp49 myotoxicphospholipase A2 from Bothrops asper snake venom: syntheticLys49 myotoxin II- (115-129) peptide identifies its bactericidalregion. Eur J Biochem 253: 452-461.30. Lee ML, Tan NH, Fung SY, Sekaran SD (2011) Antibacterial actionof a heat-stable form of L-amino acid oxidase isolated from kingcobra (Ophiophagus Hannah) venom. Comp Biochem PhysiolToxicol Pharmacol 153: 237-242.31. Samy RP, Gpalakrishnakone P, Chow VT, Ho B (2008a) Vipermetalloproteinase (Agkistrodon halys pallas) with antibacterialactivity against multi-drug resistant human pathogens. J CellPhysiol 261: 54-68.32. Nunes Edos S, de Souza MA, Vaz AF, Santana GM, Gomes FS, etal. (2011) Purification of a lectin with antibacterial activity fromBothrops leucurus snake venom. Comparative Biochemistry andPhysiology Part B 159: 57-63.33. Forst S, Weiss J, Blackburn P, Frangione B, Goni F, et al. (1986)Amino acid sequence of a basic Agkistrodon halys blomhoffiiphospholipase A2. Possible role of NH2-terminal lysines in actionon phospholipids of Escherichia coli. Biochem 25: 4309-4314.34. Soares AM, Mancin AC, Cecchini AL, Arantes EC, França SC, et al.(2001) Effects of chemical modifications of crotoxin B, thephospholipase A2 subunit of crotoxin from Crotalus durissusterrificus snake venom, on its enzymatic and pharmacologicalactivities. Int J Biochem Cell Biol 33: 877-888.35. Rodrigues VM, Marcussi S, Cambraia RS, de Araújo AL, Malta-Neto NR, et al. (2004) Bactericidal and neurotoxic activities oftwo myotoxic phospholipases A2 from Bothrops neuwiedipauloensis snake venom. Toxicon 44: 305-314.36. Roberto PG, Kashima S, Marcussi S, Pereira JO, Astolfi-Filho S, etal. (2004) Cloning and identification of a complete cDNA codingfor a bactericidal and antitumoral Acidic phospholipase A2 fromBothrops jararacussu venom. The Protein J 23: 273-285.37. Santamaría C, Larios S, Angulo Y, Pizarro-Cerda J, Gorvel JP, et al.(2005a) Antimicrobial activity of myotoxic phospholipase A2from crotalid snake venoms and synthetic peptide variantsderived from their C-terminal region. Toxicon 45: 807-815.38. Santamaría C, Larios S, Quiró S, Pizarro-Cerda J, Gorvel JP, et al.(2005b) Bactericidal and antiendotoxic properties of shortcationic peptides derived from a snake venom Lys49phosphlipase A2. Antimicrobial Agents and Chemotherapy 49:1340-1345.39. Samy RP, Gopalakrishnakone P, Ho B, Chow VTK (2008b)Purification, characterization and bactericidal activities of basicphospholipase A2 from the venom of Agkistrodon halys (Chinesepallas). Biochimie 90: 1372-1388.40. Samy RP, Gopalakrishnakone P, Bow H, Puspharaj PN, Chow VTK(2010) Identification and characterization of a phospholipase A2from the venom of the Saw-scaled viper: Novel bactericidal andmembrane damaging activities. Biochimie 92: 1854-1866.41. Samy RP, Gopalakrishnakone P, Stiles BG, Girish KS, Swamy SN,et al. (2012) Snake venom phospholipase A2: a novel tool againstbacterial diseases. Curr Med Chem 19: 6150-6162.42. Samy RP, Kandasamy M, Gopalakrishnakone P, Stiles BG, RowanEG, et al. (2014) Wound healing activity and mechanisms ofaction of an antibacterial protein from the venom of the easterndiamondback rattlesnake (Crotalus adamanteus). PLoS One 9:e80199.43. Vargas LJ, Londoño M, Quintana JC, Rua C, Segura C, et al. (2012)An acidic phospholipase A with antibacterial activity fromPorthidium nasutum snake venom. Comp Biochem Physiol BBiochem Mol Biol 161: 341-347.44. Conlon JM, Attoub S, Arafat H, Mechkarska M, Casewell NR, etal. (2013) Cytotoxic activities of [Ser] phospholipase A from thevenom of the saw-scaled vipers Echis ocellatus, Echispyramidum leakeyi, Echis carinatus sochureki, and Echiscoloratus. Toxicon 71: 96-104.45. Almeida JR, Lancellotti M, Soares AM, Calderon LA, Ramírez D,et al. (2016) CoaTx-II, a new dimeric Lys49 phospholipase A2from Crotalus oreganus abyssus snake venom with bactericidalpotential: insights into its structure and biological roles. Toxicon120: 147-158.46. Bacha AB, Alonazi MA, Elshikh MS, Karray A (2018) A novelbactericidal homodimeric PLA2 group-I from Walterinnesiaaegyptia venom. Inter J Biological Macromolecules 117:1140-1146.47. Resende LM, Almeida JR, Schezaro-Ramos R, Collaco RCO,Simioni LR, et al. (2017) Exploring and understanding thefunctional role, and biochemical and structural characteristics ofan acidic phospholipase A2, AplTx-I, purified from Agkistrodonpiscivorus leucostoma snake venom. Toxicon 127: 22-36.48. Jia Y, Villarreal J (2018) Phospholipase A2 purified fromcottonmouth snake venoms display no antibacterial effectagainst four representative bacterial species. Toxicon 151: 1-4.49. Beers SA, Buckland AG, Koduri RS, Cho W, Gelb MH, et al. (2002)The antibacterial properties of secreted phospholipase A2. J BiolChem 277: 1788-1793.Journal of Molecular SciencesVol.2 No.2:92018© Copyright iMedPub 3

Snake Venom Phospholipase A2 And Its Antibacterial Potential

https://scholarworks.utrgv.edu/cgi/viewcontent.cgi?article=1257&context=bio_fac

Snake Venom Phospholipase A2 And Its Antibacterial Potential

Abstract

Similar works

Full text

Available Versions

Scholarworks@UTRGV Univ. of Texas RioGrande Valley