Cyanovirin-N: A sugar-binding antiviral protein with a new twist

Cellular and Molecular Life Sciences

Volumn 60, Issue 2, 2003, Pages 277-287

  Botos, I ^a   Wlodawer, A ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

3D domain swapping; Anti HIV activity; Cyanovirin N; gp 120; NMR; Protein folding; X ray

Indexed keywords

ANTIVIRUS AGENT; CARBOHYDRATE BINDING PROTEIN; CYANOVIRIN N; ENVELOPE PROTEIN; NATURAL PRODUCT; VIRUS GLYCOPROTEIN;

ANTIVIRAL ACTIVITY; BINDING AFFINITY; CARBOHYDRATE SYNTHESIS; CHEMOTHERAPY; COMPLEX FORMATION; CRYSTALLOGRAPHY; CYANOBACTERIUM; DRUG ACTIVITY; DRUG MECHANISM; DRUG POTENCY; DRUG SPECIFICITY; GENE MUTATION; GENE SEQUENCE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION PREVENTION; MOLECULAR INTERACTION; NONHUMAN; NOSTOC ELLIPSOSPORUM; NUCLEAR MAGNETIC RESONANCE; PROTEIN ANALYSIS; PROTEIN DOMAIN; REVIEW; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; VIRUS ENVELOPE; VIRUS INFECTION; WILD TYPE;

ANTI-HIV AGENTS; BACTERIAL PROTEINS; CARRIER PROTEINS; CRYSTALLOGRAPHY, X-RAY; DIMERIZATION; HIV ENVELOPE PROTEIN GP120; HIV INFECTIONS; HIV-1; HUMANS; IMAGING, THREE-DIMENSIONAL; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTATION; PROTEIN STRUCTURE, TERTIARY;

HUMAN IMMUNODEFICIENCY VIRUS; NOSTOC; NOSTOC ELLIPSOSPORUM; NOSTOC SP.;

EID: 0037300816     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s000180300023     Document Type: Review

References (62)

1. Demain A. L. (1999) Pharmaceutically active secondary metabolites of microorganisms. Appl. Microbiol. Biotechnol. 52: 455-463
2. O'Keefe B. R. (2001) Biologically active proteins from natural product extracts. J. Nat. Prod. 64: 1373-1381
3. Boyd M. R., Gustafson K. R., McMahon J. B., Shoemaker R. H., O'Keefe B. R., Mori T et al. (1997) Discovery of cyanovirin-N, a novel human immunodeficiency virus- inactivating protein that binds viral surface envelope glycoprotein gp 120: potential applications to microbicide development. Antimicrob. Agents Chemother. 41: 1521-1530
4. De Clercq E. (2000) Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med. Res. Rev. 20: 323-349
5. Mori T., Gustafson K. R., Pannell L. K., Shoemaker R. H., Wu L., McMahon J. B. et al. (1998) Recombinant production of cyanovirin-N, a potent human immunodeficiency virus-inactivating protein derived from a cultured cyanobacterium. Protein Expr. Purif. 12: 151-158
6. Dey B., Lerner D. L., Lusso P., Boyd M. R., Elder J. H. and Berger E. A. (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
7. O'Keefe B. R., Shenoy S. R., Xie D., Zhang W., Muschik J. M., Currens M. J. et al. (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
8. Bergsma J., Hol W. G., Jansonius J. N., Kalk K. H., Ploegman J. H. and Smit J. D. (1975) The double domain structure of rhodanese. J. Mol. Biol. 98: 637-643
9. Gustafson K. R., Sowder R. C., Henderson L. E., Cardellina J. H., McMahon J. B., Rajamani U. et al. (1997) Isolation, primary sequence determination and disulfide bond structure of cyanovirin-N, an anti-HIV (human immunodeficiency virus) protein from the cyanobacterium Nostoc ellipsosporum. Biochem. Biophys. Res. Commun. 238: 223-228
10. Bewley C. A., Gustafson K. R., Boyd M. R., Covell D. G., Bax A., Clore G. M. et al. (1998) Solution structure of cyanovirin-N, a potent HIV-inactivating protein. Nat. Struct. Biol. 5: 571-578
11. Bewley C. A. (2001) Solution structure of a cyanovirin-N: Man alpha 1-2Man alpha complex: structural basis for high-affinity carbohydrate-mediated binding to gp120. Structure. (Camb.) 9: 931-940
12. Barrientos L. G., Campos-Olivas R., Louis J. M., Fiser A., Sali A. and Gronenborn A. M. (2001) 1H, 13C, 15N resonance assignments and fold verification of a circular permuted variant of the potent HIV-inactivating protein cyanovirin-N. J. Biomol. NMR 19: 289-290
13. Clore G. M. and Bewley C. A. (2002) Using conjoined rigid body/torsion angle simulated annealing to determine the relative orientation of covalently linked protein domains from dipolar couplings. J. Magn. Reson. 154: 329-335
14. Barrientos L., Louis J. M., Botos I., Mori T., Han Z., O'Keefe B. R. et al. (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
15. Yang F., Bewley C. A., Louis J. M., Gustafson K. R., Boyd M. R., Gronenborn A. M. et al. (1999) Crystal structue of cyanovirin-N, a potent HIV-inactivating protein, shows unexpected domain swapping. J. Mol. Biol. 288: 403-412
16. Botos I., Mori T., Cartner L. K., Boyd M. R. and Wlodawer A. (2002) Domain-swapped structure of a mutant of cyanovirin-N. Biochem. Biophys. Res. Commun. 294: 184-190
17. Botos I., O'Keefe B. R., Shenoy S. R., Cartner L. K., Ratner D. M., Seeberger P. H. et al. (2002) Structures of the complexes of a potent anti-HIV protein cyanovirin-N and high-mannose oligosaccharides. J. Biol. Chem. 277: 1-7
18. Clore G. M. and Gronenborn A. M. (1998) New methods of structure refinement for macromolecular structure determination by NMR. Proc. Natl. Acad. Sci. USA 95: 5891-5898
19. Gooptu B., Hazes B., Chang W. S., Dafforn T. R., Carrell R. W., Read R. J. et al. (2000) Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease. Proc. Natl. Acad. Sci. USA 97: 67-72
20. Bewley C. A. and Clore G. M. (2000) Determination of the relative orientation of the two halves of the domain-swaped dimer of cyanovirin-N in solution using dipolar couplings and rigid body minimization. J. Am. Chem. Soc. 122: 6009-6016
21. Holm L. and Sander C. (1993) Protein structure comparison by alignment of distance matrices. J. Mol. Biol. 233: 123-138
22. Edmondson S. P., Qiu L. and Shriver J. W. (1995) Solution structure of the DNA-binding protein Sac7d from the hyperthermophile Sulfolobus acidocaldarius. Biochemistry 34: 13289-13304
23. Kuriyan J. and Cowburn D. (1993) Structures of SH2 and SH3 domains. Curr. Opin. Struct. Biol. 3: 828-837
24. Bennett M. J., Schlunegger M. P. and Eisenberg D. (1995) 3D domain swapping: a mechanism for oligomer assembly. Protein Sci. 4: 2455-2468
25. MacArthur M. W. and Thornton J. M. (1991) Influence of proline residues on protein conformation. J. Mol. Biol. 218: 397-412
26. Rousseau F., Schymkowitz J. W., Wilkinson H. R. and Itzhaki L. S. (2001) Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues. Proc. Natl. Acad. Sci. USA 98: 5596-5601
27. Bewley C. A. and Otero-Quintero S. (2001) The potent anti-HIV protein cyanovirin-N contains two novel carbohydrate binding sites that selectively bind to Man(8) D1D3 and Man(9) with nanomolar affinity: implications for binding to the HIV envelope protein gp120. J. Am. Chem. Soc. 123: 3892-3902
28. Bolmstedt A. J., O'Keefe B. R., Shenoy S. R., McMahon J. B. and Boyd M. R. (2001) Cyanovirin-N defines a new class of antiviral agent targeting N-linked, high-mannose glycans in an oligosaccharide-specific manner. Mol. Pharmacol. 59: 949-954
29. Hadden J. M., Convery M. A., Declais A. C., Lilley D. M. and Phillips S. E. (2001) Crystal structure of the Holliday junction resolving eazyme T7 endonuclease I. Nat. Struct. Biol. 8: 62-67
30. Declais A. C., Hadden J., Phillips S. E. and Lilley D. M. (2001) The active site of the junction-resolving enzyme T7 endonuclease I. J. Mol. Biol. 307: 1145-1158
31. Chen Y., Narendra U., Iype L. E., Cox M. M. and Rice P. A. (2000) Crystal structure of a Flp recombinase-Holliday junction complex: assembly of an active oligomer by helix swapping. Mol. Cell 6: 885-897
32. Mariner J. M., McMahon J. B., O'Keefe B. R., Nagashima K. and Boyd M. R. (1998) The HIV-inactivating protein, cyanovirin-N, does not block gp120- mediated virus-to-cell binding. Biochem Biophys. Res. Commun. 248: 841-845
33. Esser M. T., Mori T., Mondor I., Sattentau Q. J., Dey B., Berger E. A. et al. (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
34. Mori T., Shoemaker R. H., Gulakowski R. J., Krepps B. L., McMahon J. B., Gustafson K. R. et al. (1997) Analysis of sequence requirements for biological activity of cyanovirin-N, a potent HIV (human immunodeficiency virus)- inactivating protein. Biochem. Biophys. Res. Commun. 238: 218-222
35. Han Z., Xiong C., Mori T. and Boyd M. R. (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
36. Kelley B. S., Chang L. C. and Bewley C. A. (2002) Engineering an obligate domain-swapped dimer of cyanovirin-N with enhanced anti-HIV activity. J. Am. Chem. Soc. 124: 3210-3211
37. Chang L. C. and Bewley C. A. (2002) Potent inhibition of HIV-1 fusion by cyanovirin-N requires only a single high affinity carbohydrate binding site: characterization of low-affinity carbohydrate binding site knockout mutants. J. Mol. Biol. 318: 1-8
38. Nussbaum O., Broder C. C. and Berger E. A. (1994) Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J. Virol. 68: 5411-5422
39. Bewley C. A. (2001) Rapid validation of the overall structure of an internal domain-swapped mutant of the anti-HIV protein cyanovirin-N using residual dipolar couplings. J. Am. Chem. Soc. 123: 1014-1015
40. Barrientos L. G., Louis J. M., Hung J., Smith T. H., O'Keefe B. R., Gardella R. S. et al. (2002) Design and initial characterization of a circular permuted variant of the potent HIV-inactivating protein cyanovirin-N. Proteins 46: 153-160
41. Mori T. and Boyd M. R. (2001) Cyanovirin-N, a potent human immunodeficiency virus-inactivating protein, blocks both CD4-dependent and CD4-independent binding of soluble gp120 (sgp120) to target cells, inhibits sCD4-induced binding of sgp120 to cell-associated CXCR4, and dissociates bound sgp120 from target cells. Antimicrob. Agents Chemother. 45: 664-672
42. Shenoy S. R., O'Keefe B. R., Bolmstedt A. J., Cartner L. K. and Boyd M. R. (2001) Selective interactions of the human immunodeficiency virus-inactivating protein cyanovirin-N with highmannose oligosaccharides on gp120 and other glycoproteins. J. Pharmacol. Exp. Ther. 297: 704-710
43. Hu N. T., Thiel T., Giddings T. H. Jr and Wolk C. P. ( 1981) New Anabaena and Nostoc cyanophages from sewage settling ponds. Virology 114: 236-246
44. Sherman L. A. and Connelly M. (1976) Isolation and characterization of a cyanophage infecting the unicellular blue-green algae A. nidulans and S. cedrorum. Virology 72: 540-544
45. Adolph K. W. and Haselkorn R. (1972) Photosynthesis and the development of blue-green algal virus N-1. Virology 47: 370-374
46. Safferman R. S., Morris M. E., Sherman L. A. and Haselkorn R. (1969) Serological and electron microscopic characterization of a new group of blue-green algal viruses (LPP-2). Virol. 39: 775-780
47. Rice K. G. and Lee Y. C. (1993) Oligosaccharide valency and conformation in determining binding to the asialoglycoprotein receptor of rat hepatocytes. Adv. Enzymol. Relat Areas Mol. Biol. 66: 41-83
48. Dimick S. M., Powel S. C., McMahon S. A., Moothoo D. N., Haismith J. H. and Toone E. J. (2002) On the meaning of affinity: cluster glycoside effects and concanavalin A. J. Am. Chem. Soc 121: 10286-10296
49. Piot P. (1998) The science of AIDS: a tale of two worlds. Science 280: 1844-1845
50. Burton D. R. (1997) A vaccine for HIV type 1: the antibody perspective. Proc. Natl. Acad. Sci. USA 94: 10018-10023
51. Heilman C. A. and Baltimore D. (1998) HIV vaccines - where are we going? Nat. Med. 4: 532-534
52. Lange J. M., Karam M. and Piot P. (1993) Boost for vaginal microbicides against HIV. Lancet 342: 1356
53. Mori T., Shoemaker R. H., McMahon J. B., Gulakowski R. J., Gustafson K. R. and Boyd M. R. (1997) Construction and enhanced cytotoxicity of a [cyanovirin-N]- [Pseudomonas exotoxin] conjugate against human immunodeficiency virus-infected cells. Biochem Biophys. Res. Commun. 239: 884-888
54. Gandhi M. J., Boyd M. R., Yi L., Yang G. G. and Vyas G. N (2000) Properties of cyanovirin-N (CV-N): inactivation of HIV-1 by sessile cyanovirin-N (sCV-N). Dev. Biol. Stand. 102: 141-148
55. Giomarelli B., Provvedi R., Meacci F., Maggi T., Medaglini D., Mori T. et al. (2002) The microbicide cyanovirin-N expressed in the surface of commensal bacterium Streptococcus gordonii captures HIV-1. AIDS 16: 1351-1356
56. Oggioni M. R., Manganelli R., Contorni M., Tommasino M. and Pozzi G. (1995) Immunization of mice by oral colonization with live recombinant commensal streptococci. Vaccine 13: 775-779
57. Esnouf R. M. (1997) An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J. Mol. Graph. Model. 15: 132-134
58. Meritt E. A. and Murphy M. E. P. (1994) Raster3D Version 2.0. A program for photorealistic molecular graphics. Acta. Crystallogr. D50: 869-873
59. Cohen G. E. (1997) ALIGN: a program to superimpose protein coordinates, accounting for insertions and deletions. J. Appl. Crystallogr. 30: 1160-1161
60. Christopher, J. A. (1998) SPOCK: The Structural Properties Observation and Calculation Kit. The Center for Macromolecular Design, Texas A&M University, College Station, TX
61. Nicholls, A. (1992) GRASP: Graphical Representation and Analysis of Surface Properties. Columbia University, New York
62. Gulakowski R. J., McMahon J. B., Staley P. G., Moran R. A. and Boyd M. R. (1991) A semi automated multiparameter approach for anti-HIV drug screening. J. Virol. Methods 33: 87-100