Structural studies of algal lectins with anti-HIV activity

• Authors: Natasza E Ziółkowska , Alexander Wlodawer
• Languages of publication: EN

Abstracts

EN

A number of antiviral lectins, small proteins that bind carbohydrates found on viral envelopes, are currently in pre-clinical trials as potential drugs for prevention of transmission of human immunodeficiency virus (HIV) and other enveloped viruses, such as the Ebola virus and the coronavirus responsible for severe acute respiratory syndrome (SARS). Lectins of algal origin whose antiviral properties make them candidate agents for prevention of viral transmission through topical applications include cyanovirin-N, Microcystis viridis lectin, scytovirin, and griffithsin. Although all these proteins exhibit significant antiviral activity, their structures are unrelated and their mode of binding of carbohydrates differs significantly. This review summarizes the current state of knowledge of the structures of algal lectins, their mode of binding of carbohydrates, and their potential medical applications.

Keywords

EN

topical antivirals; protein structure; HIV; lectin; AIDS

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2006
• Volume: 53
• Issue: 4
• Pages: 617-626

Dates

published

2006

received

2006-10-10

revised

2006-11-18

accepted

2006-11-20

(unknown)

2006-11-27

Contributors

author

Natasza E Ziółkowska

• Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA

author

Alexander Wlodawer

• Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD, USA

References

• Adams EW, Ueberfeld J, Ratner DM, O'Keefe BR, Walt DR, Seeberger PH (2003) Encoded fiber-optic microsphere arrays for probing protein-carbohydrate interactions. Angew Chem Int Ed Engl 42: 5317-5320.
• Aucouturier P, Mihaesco E, Mihaesco C, Preud'Homme JL (1987) Characterization of jacalin, the human IgA and IgD binding lectin from jackfruit. Mol Immunol 24: 503-511.
• Balzarini J (2006) Inhibition of HIV entry by carbohydrate-binding proteins. Antiviral Res 71: 237-247.
• Balzarini J, Schols D, Neyts J, Van Damme E, Peumans W, De Clercq E (1991) Alpha-(1-3)- and alpha-(1-6)-D-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro. Antimicrob Agents Chemother 35: 410-416.
• Balzarini J, Neyts J, Schols D, Hosoya M, Van Damme E, Peumans W, De Clercq E (1992) The mannose-specific plant lectins from Cymbidium hybrid and Epipactis helleborine and the (N-acetylglucosamine)n-specific plant lectin from Urtica dioica are potent and selective inhibitors of human immunodeficiency virus and cytomegalovirus replication in vitro. Antiviral Res 18: 191-207.
• Barrientos L, Louis JM, Botos I, Mori T, Han Z, O'Keefe BR, Boyd MR, Wlodawer A, Gronenborn A (2002) The domain-swapped dimer of cyanovirin-N is in a metastable folded state. Reconcilliation of X-ray and NMR structures. Structure 10: 673-686.
• Barrientos LG, O'Keefe BR, Bray M, Sanchez A, Gronenborn AM, Boyd MR (2003) Cyanovirin-N binds to the viral surface glycoprotein, GP1,2> and inhibits infectivity of Ebola virus. Antiviral Res 58: 47-56.
• Barrientos LG, Gronenborn AM (2005) The highly specific carbohydrate-binding protein cyanovirin-N: structure, anti-HIV/Ebola activity and possibilities for therapy. Mini Rev Med Chem 5: 21-31.
• Bennett MJ, Schlunegger MP, Eisenberg D (1995) 3D domain swapping: a mechanism for oligomer assembly. Protein Sci 4: 2455-2468.
• Bewley CA, Gustafson KR, Boyd MR, Covell DG, Bax A, Clore GM, Gronenborn AM (1998) Solution structure of cyanovirin-N, a potent HIV-inactivating protein. Nature Struct Biol 5: 571-578.
• Bewley CA (2001) Solution structure of a cyanovirin-N:Manα 1-2Manα complex: structural basis for high-affinity carbohydrate-mediated binding to gp120. Structure 9: 931-940.
• Bewley CA, Cai M, Ray S, Ghirlando R, Yamaguchi M, Muramoto K (2004) New carbohydrate specificity and HIV-1 fusion blocking activity of the cyanobacterial protein MVL: NMR, ITC and sedimentation equilibrium studies. J Mol Biol 339: 901-914.
• Bokesch HR, O'Keefe BR, McKee TC, Pannell LK, Patterson GM, Gardella RS, Sowder RC, Turpin J, Watson K, Buckheit RW, Jr., Boyd MR (2003) A potent novel anti-HIV protein from the cultured cyanobacterium Scytonema varium. Biochemistry 42: 2578-2584.
• Botos I, Wlodawer A (2005) Proteins that bind high-mannose sugars of the HIV envelope. Prog Biophys Mol Biol 88: 233-282.
• Botos I, Mori T, Cartner LK, Boyd MR, Wlodawer A (2002a) Domain-swapped structure of a mutant of cyanovirin-N. Biochem Biophys Res Commun 294: 184-190.
• Botos I, O'Keefe BR, Shenoy SR, Cartner LK, Ratner DM, Seeberger PH, Boyd MR, Wlodawer A (2002b) Structures of the complexes of a potent anti-HIV protein cyanovirin-N and high mannose oligosaccharides. J Biol Chem 277: 34336-42.
• Bourne Y, Zamboni V, Barre A, Peumans WJ, Van Damme EJ, Rouge P (1999) Helianthus tuberosus lectin reveals a widespread scaffold for mannose-binding lectins. Structure Fold Des 7: 1473-1482.
• Boyd MR, Gustafson KR, McMahon JB, Shoemaker RH, O'Keefe BR, Mori T, Gulakowski RJ, Wu L, Rivera MI, Laurencot CM, Currens MJ, Cardellina JH, Buckheit RW, Jr., Nara PL, Pannell LK, Sowder RC, Henderson LE (1997) Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrob Agents Chemother 41: 1521-1530.
• Calarese DA, Scanlan CN, Zwick MB, Deechongkit S, Mimura Y, Kunert R, Zhu P, Wormald MR, Stanfield RL, Roux KH, Kelly JW, Rudd PM, Dwek RA, Katinger H, Burton DR, Wilson IA (2003) Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 300: 2065-2071.
• Chandra N (2006) Common scaffolds, diverse recognition profiles. Structure 14: 1093-1094.
• Charan RD, Munro MH, O'Keefe BR, Sowder RCII, McKee TC, Currens MJ, Pannell LK, Boyd MR (2000) Isolation and characterization of Myrianthus holstii lectin, a potent HIV-1 inhibitory protein from the plant Myrianthus holstii. J Nat Prod 63: 1170-1174.
• Chothia C, Murzin AG (1993) New folds for all-β proteins. Structure 1: 217-22.
• De Clercq E (2005) Emerging anti-HIV drugs. Expert Opin Emerg Drugs 10: 241-273.
• De Mejia EG, Prisecaru VI (2005) Lectins as bioactive plant proteins: a potential in cancer treatment. Crit Rev Food Sci Nutr 45: 425-445.
• Dey B, Lerner DL, Lusso P, Boyd MR, Elder JH, Berger EA (2000) Multiple antiviral activities of cyanovirin-N: blocking of human immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and inhibition of diverse enveloped viruses. J Virol 74: 4562-4569.
• Esser MT, Mori T, Mondor I, Sattentau QJ, Dey B, Berger EA, Boyd MR, Lifson JD (1999) Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120. J Virol 73: 4360-4371.
• Gabius HJ (1997) Animal lectins. Eur J Biochem 243: 543-576.
• Giomarelli B, Provvedi R, Meacci F, Maggi T, Medaglini D, Mori T, McMahon JB, Gardella R, Boyd MR (2002) The microbicide cyanovirin-N expressed in the surface of commensal bacterium Streptococcus gordonii captures HIV-1. AIDS 16: 1351-1360.
• Giomarelli B, Schumacher KM, Taylor TE, Sowder RC, Hartley JL, McMahon JB, Mori T (2006) Recombinant production of anti-HIV protein, griffithsin, by auto-induction in a fermentor culture. Protein Expr Purif 47: 194-202.
• Han Z, Xiong C, Mori T, Boyd MR (2002) Discovery of a stable dimeric mutant of cyanovirin-N (CV-N) from a T7 phage-displayed CV-N mutant library. Biochem Biophys Res Commun 292: 1036-1043.
• Hansen JE, Nielsen CM, Nielsen C, Heegaard P, Mathiesen LR, Nielsen JO (1989) Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins. AIDS 3: 635-641.
• Harata K, Muraki M (2000) Crystal structures of Urtica dioica agglutinin and its complex with tri-N-acetylchitotriose. J Mol Biol 297: 673-681.
• Helle F, Wychowski C, Vu-Dac N, Gustafson KR, Voisset C, Dubuisson J (2006) Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein glycans. J Biol Chem 281: 25177-25183.
• Jeyaprakash AA, Srivastav A, Surolia A, Vijayan M (2004) Structural basis for the carbohydrate specificities of artocarpin: variation in the length of a loop as a strategy for generating ligand specificity. J Mol Biol 338: 757-770.
• Ji X, Chen Y, Faro J, Gewurz H, Bremer J, Spear GT (2006) Interaction of human immunodeficiency virus (HIV) glycans with lectins of the human immune system. Curr Protein Pept Sci 7: 317-234.
• Lis H, Sharon N (1998) Lectins: Carbohydrate-specific proteins that mediate cellular recognition. Chem Rev 98: 637-674.
• Meagher JL, Winter HC, Ezell P, Goldstein IJ, Stuckey JA (2005) Crystal structure of banana lectin reveals a novel second sugar binding site. Glycobiology 15: 1033-1042.
• Mizuochi T, Spellman MW, Larkin M, Solomon J, Basa LJ, Feizi T (1988) Carbohydrate structures of the human-immunodeficiency-virus (HIV) recombinant envelope glycoprotein gp120 produced in Chinese-hamster ovary cells. Biochem J 254: 599-603.
• Mori T, Gustafson KR, Pannell LK, Shoemaker RH, Wu L, McMahon JB, Boyd MR (1998) Recombinant production of cyanovirin-N, a potent human immunodeficiency virus-inactivating protein derived from a cultured cyanobacterium. Protein Expr Purif 12: 151-158.
• Mori T, O'Keefe BR, Sowder RC, Bringans S, Gardella R, Berg S, Cochran P, Turpin JA, Buckheit RW, Jr., McMahon JB, Boyd MR (2005) Isolation and characterization of griffithsin, a novel HIV-inactivating protein, from the red alga Griffithsia sp. J Biol Chem 280: 9345-9353.
• O'Keefe BR (2001) Biologically active proteins from natural product extracts. J Nat Prod 64: 1373-1381.
• O'Keefe BR, Beutler JA, Cardellina JH, Gulakowski RJ, Krepps BL, McMahon JB, Sowder RC, Henderson LE, Pannell LK, Pomponi SA, Boyd MR (1997) Isolation and characterization of niphatevirin, a human-immunodeficiency-virus-inhibitory glycoprotein from the marine sponge Niphates erecta. Eur J Biochem 245: 47-53.
• O'Keefe BR, Shenoy SR, Xie D, Zhang W, Muschik JM, Currens MJ, Chaiken I, Boyd MR (2000) Analysis of the interaction between the HIV-inactivating protein cyanovirin-N and soluble forms of the envelope glycoproteins gp120 and gp41. Mol Pharmacol 58: 982-992.
• O'Keefe BR, Smee DF, Turpin JA, Saucedo CJ, Gustafson KR, Mori T, Blakeslee D, Buckheit R, Boyd MR (2003) Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin. Antimicrob Agents Chemother 47: 2518-2525.
• Raval S, Gowda SB, Singh DD, Chandra NR (2004) A database analysis of jacalin-like lectins: sequence-structure-function relationships. Glycobiology 14: 1247-1263.
• Reeves JD, Piefer AJ (2005) Emerging drug targets for antiretroviral therapy. Drugs 65: 1747-1766.
• Sacchettini JC, Baum LG, Brewer CF (2001) Multivalent protein-carbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction. Biochemistry 40: 3009-3015.
• Shenoy SR, Barrientos LG, Ratner DM, O'Keefe BR, Seeberger PH, Gronenborn AM, Boyd MR (2002) Multisite and multivalent binding between cyanovirin-N and branched oligomannosides: calorimetric and NMR characterization. Chem Biol 9: 1109-1118.
• Shimizu T, Morikawa K (1996) The β-prism: a new folding motif. Trends Biochem Sci 21: 3-6.
• Tsai CC, Emau P, Jiang Y, Tian B, Morton WR, Gustafson KR, Boyd MR (2003) Cyanovirin-N gel as a topical microbicide prevents rectal transmission of SHIV89.6P in macaques. AIDS Res Hum Retroviruses 19: 535-541.
• Tsai CC, Emau P, Jiang Y, Agy MB, Shattock RJ, Schmidt A, Morton WR, Gustafson KR, Boyd MR (2004) Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses 20: 11-18.
• Turpin JA (2002) Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. Expert Opin Investig Drugs 11: 1077-1097.
• Tziveleka LA, Vagias C, Roussis V (2003) Natural products with anti-HIV activity from marine organisms. Curr Top Med Chem 3: 1512-1535.
• Weis WI, Drickamer K (1996) Structural basis of lectin-carbohydrate recognition. Annu Rev Biochem 65: 441-473.
• Williams DC, Jr., Lee JY, Cai M, Bewley CA, Clore GM (2005) Crystal structures of the HIV-1 inhibitory cyanobacterial protein MVL free and bound to Man3>GlcNAc2>: structural basis for specificity and high-affinity binding to the core pentasaccharide from n-linked oligomannoside. J Biol Chem 280: 29269-29276.
• Xiong C, O'Keefe BR, Botos I, Wlodawer A, McMahon JB (2006) Overexpression and purification of scytovirin, a potent, novel anti-HIV protein from the cultured cyanobacterium Scytonema varium. Protein Expr Purif 46: 233-239.
• Yamaguchi M, Ogawa T, Muramoto K, Kamio Y, Jimbo M, Kamiya H (1999) Isolation and characterization of a mannan-binding lectin from the freshwater cyanobacterium (blue-green algae) Microcystis viridis. Biochem Biophys Res Commun 265: 703-708.
• Yang F, Bewley CA, Louis JM, Gustafson KR, Boyd MR, Gronenborn AM, Clore GM, Wlodawer A (1999) Crystal structure of cyanovirin-N, a potent HIV-inactivating protein, shows unexpected domain swapping. J Mol Biol 288: 403-142.
• Ziółkowska NE, O'Keefe BR, Mori T, Zhu C, Giomarelli B, Vojdani F, Palmer KE, McMahon JB, Wlodawer (2006) Domain-swapped structure of the potent antiviral protein griffithsin and its mode of carbohydrate binding. Structure 14: 1127-1135.
• Ziółkowska NE, Shenoy SR, O'Keefe BR, McMahon JB, Palmer KE, Dwek RA, Wormald MR, Wlodawer A (2007) Crystallographic, thermodynamic, and molecular modeling studies of the mode of binding of oligosaccharides to the potent antiviral protein griffithsin. Proteins: Struct Funct Bioinform, in press.