Document Detail


Carbohydrate recognition by the antiviral lectin cyanovirin-N.
MedLine Citation:
PMID:  23057413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyanovirin-N (CVN) is a cyanobacterial lectin with potent antiviral activity and has been the focus of extensive preclinical investigation as a potential prophylactic for the prevention of the sexual transmission of the human immunodeficiency virus (HIV). Here we present a detailed analysis of carbohydrate recognition by this important protein, using a combination of computational methods, including extensive molecular dynamics simulations and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) energetic analysis. The simulation results strongly suggest that the observed tendency of wild-type CVN to form domain-swapped dimers is the result of a previously unidentified cis-peptide bond present in the monomeric state. The energetic analysis additionally indicates that the highest-affinity ligand for CVN characterized to date (α-Man-(1,2)-α-Man-(1,2)-α-Man) is recognized asymmetrically by the two binding sites. Finally, we are able to provide a detailed map of the role of all binding site functional groups (both backbone and side chain) to various aspects of molecular recognition: general affinity for cognate ligands, specificity for distinct oligosaccharide targets, and the asymmetric recognition of α-Man-(1,2)-α-Man-(1,2)-α-Man. Taken as a whole, these results complement past experimental characterization (both structural and thermodynamic) to provide the most complete understanding of carbohydrate recognition by CVN to date. The results also provide strong support for the application of similar approaches to the understanding of other protein-carbohydrate complexes.
Authors:
Yukiji K Fujimoto; David F Green
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-20
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  134     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-05     Completed Date:  2013-05-20     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19639-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Bacterial Proteins / chemistry,  therapeutic use*
Binding Sites
Carbohydrates / chemistry*
Carrier Proteins / chemistry,  therapeutic use*
HIV Envelope Protein gp120 / chemistry
Humans
Lectins / chemistry,  therapeutic use*
Ligands
Magnetic Resonance Spectroscopy
Models, Molecular
Grant Support
ID/Acronym/Agency:
R01 GM086199/GM/NIGMS NIH HHS; R01-GM086199/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Carbohydrates; 0/Carrier Proteins; 0/HIV Envelope Protein gp120; 0/Lectins; 0/Ligands; 184539-38-6/cyanovirin N
Comments/Corrections

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