![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 297, Issue 2, 704-710, May 2001
Laboratory of Drug Discovery Research and Development, NCI Center
for Cancer Research, National Cancer Institute, Frederick, Maryland
(S.R.S., B.R.O., M.R.B.); Department of Clinical Virology, University
of Göteborg, Göteborg, Sweden (A.J.B.); and SAIC-Frederick,
Frederick, Maryland (L.K.C.)
The virucidal protein cyanovirin-N (CV-N) mediates its highly
potent anti-human immunodeficiency virus activity, at least in
part, through interactions with the viral envelope glycoprotein gp120.
Here we dissect in further detail the mechanism of CV-N's glycosylation-dependent binding to gp120. Isothermal titration calorimetry (ITC) binding studies of CV-N with endoglycosidase H-treated gp120 showed that binding was completely abrogated by removal
of high-mannose oligosaccharides from the glycoprotein. Additional ITC
and circular dichroism spectral studies with CV-N and other
glycoproteins as well showed that CV-N discriminately bound only
glycoproteins that contain high-mannose oligosaccharides. Binding
experiments with RNase B indicated that the single high-mannose oligosaccharide on that enzyme mediated all of its binding with CV-N
(Kd = 0.602 µM). A finer level of
oligosaccharide selectivity of CV-N was revealed in affinity
chromatography-liquid chromatography-mass spectrometry experiments,
which showed that CV-N preferentially bound only oligomannose-8 (Man-8)
and oligomannose-9 isoforms of RNase B. Finally, we biophysically
characterized the interaction of CV-N with a purified, single
oligosaccharide, Man-8. The binding affinity of Man-8 for CV-N is
unusually strong (Kd = 0.488 µM), several hundredfold greater than observed for oligosaccharides and
their protein lectins (Kd = 1 µM-1
mM), further establishing a critical role of high-mannose
oligosaccharides in CV-N binding to glycoproteins.
This article has been cited by other articles:
|
|
 |
|
  V. Buffa, D. Stieh, N. Mamhood, Q. Hu, P. Fletcher, and R. J. Shattock Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models J. Gen. Virol., January 1, 2009; 90(1): 234 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hori, Y. Sato, K. Ito, Y. Fujiwara, Y. Iwamoto, H. Makino, and A. Kawakubo Strict specificity for high-mannose type N-glycans and primary structure of a red alga Eucheuma serra lectin Glycobiology, May 1, 2007; 17(5): 479 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, L. A. Lagenaur, D. A. Simpson, K. P. Essenmacher, C. L. Frazier-Parker, Y. Liu, D. Tsai, S. S. Rao, D. H. Hamer, T. P. Parks, et al. Engineered vaginal lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N. Antimicrob. Agents Chemother., October 1, 2006; 50(10): 3250 - 3259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Helle, C. Wychowski, N. Vu-Dac, K. R. Gustafson, C. Voisset, and J. Dubuisson Cyanovirin-N Inhibits Hepatitis C Virus Entry by Binding to Envelope Protein Glycans J. Biol. Chem., September 1, 2006; 281(35): 25177 - 25183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Doncel Exploiting common targets in human fertilization and HIV infection: development of novel contraceptive microbicides Hum. Reprod. Update, March 1, 2006; 12(2): 103 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Witvrouw, V. Fikkert, A. Hantson, C. Pannecouque, B. R. O'Keefe, J. McMahon, L. Stamatatos, E. de Clercq, and A. Bolmstedt Resistance of Human Immunodeficiency Virus Type 1 to the High-Mannose Binding Agents Cyanovirin N and Concanavalin A J. Virol., June 15, 2005; 79(12): 7777 - 7784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yasin, W. Wang, M. Pang, N. Cheshenko, T. Hong, A. J. Waring, B. C. Herold, E. A. Wagar, and R. I. Lehrer {theta} Defensins Protect Cells from Infection by Herpes Simplex Virus by Inhibiting Viral Adhesion and Entry J. Virol., May 15, 2004; 78(10): 5147 - 5156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Vermeire and D. Schols Specific CD4 down-modulating compounds with potent anti-HIV activity J. Leukoc. Biol., November 1, 2003; 74(5): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. O'Keefe, D. F. Smee, J. A. Turpin, C. J. Saucedo, K. R. Gustafson, T. Mori, D. Blakeslee, R. Buckheit, and M. R. Boyd Potent Anti-Influenza Activity of Cyanovirin-N and Interactions with Viral Hemagglutinin Antimicrob. Agents Chemother., August 1, 2003; 47(8): 2518 - 2525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W.-P. Hong, K. B. Flummerfelt, A. de Parseval, K. Gurney, J. H. Elder, and B. Lee Human Immunodeficiency Virus Envelope (gp120) Binding to DC-SIGN and Primary Dendritic Cells Is Carbohydrate Dependent but Does Not Involve 2G12 or Cyanovirin Binding Sites: Implications for Structural Analyses of gp120-DC-SIGN Binding J. Virol., November 13, 2002; 76(24): 12855 - 12865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Botos, B. R. O'Keefe, S. R. Shenoy, L. K. Cartner, D. M. Ratner, P. H. Seeberger, M. R. Boyd, and A. Wlodawer Structures of the Complexes of a Potent Anti-HIV Protein Cyanovirin-N and High Mannose Oligosaccharides J. Biol. Chem., September 6, 2002; 277(37): 34336 - 34342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Beutler, J. B. McMahon, T. R. Johnson, B. R. O'Keefe, R. A. Buzzell, D. Robbins, R. Gardella, J. Wilson, and M. R. Boyd High Throughput Screening for Cyanovirin-N Mimetics Binding to HIV-1 gp4l J Biomol Screen, April 1, 2002; 7(2): 105 - 110. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
