Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp.

Mori, Toshiyuki; O’Keefe, Barry R.; Sowder, Raymond C.; Bringans, Scott; Gardella, Roberta S.; Berg, Shannon; Cochran, Pamela K.; Turpin, Jim A.; Buckheit, Robert W.; McMahon, James B.; Boyd, Michael R.

doi:10.1074/jbc.m411122200

Cited by 399 publications

(476 citation statements)

References 45 publications

(43 reference statements)

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“…Various lectins, including cyanovirin-N (6), DC-SIGN (7), scytovirin (8), griffithsin (9), MVL (10), and actinohivin (11), are known to bind to the high mannose glycans on gp120, thereby exerting anti-HIV activity. Interestingly, the binding modes and target epitopes on Man-9 are quite distinct for the different lectins.…”

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confidence: 99%

Novel Fold and Carbohydrate Specificity of the Potent Anti-HIV Cyanobacterial Lectin from Oscillatoria agardhii

Koharudin

Furey

Gronenborn

2011

Journal of Biological Chemistry

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Oscillatoria agardhii agglutinin (OAA) is a recently discovered cyanobacterial lectin that exhibits potent anti-HIV activity. Up to now, only its primary structure and carbohydrate binding data have been available. To elucidate the structural basis for the antiviral mechanism of OAA, we determined the structure of this lectin by x-ray crystallography at 1.2 Å resolution and mapped the specific carbohydrate recognition sites of OAA by NMR spectroscopy. The overall architecture of OAA comprises 10 ␤-strands that fold into a single, compact, ␤-barrel-like domain, creating a unique topology compared with all known protein structures in the Protein Data Bank. OAA sugar binding was tested against Man-9 and various disaccharide components of Man-9. Two symmetric carbohydratebinding sites were located on the protein, and a preference for Man␣(1-6)Man-linked sugars was found. Altogether, our structural results explain the antiviral activity OAA and add to the growing body of knowledge about antiviral lectins.HIV infection occurs via virus-cell and cell-cell fusion mediated by the two viral envelope glycoproteins gp120 and gp41 (1-3). gp120 interacts with the CD4 receptor of the host cell, resulting in a conformational change in gp120 that eventually leads to the insertion of the fusion peptide of gp41 into the target membrane, causing membrane fusion (4). The gp120 glycoprotein is remarkably enriched in high mannose N-linked sugars (5), and novel avenues for controlling HIV infection may become available by targeting to the sugars of gp120.Various lectins, including cyanovirin-N (6), DC-SIGN (7), scytovirin (8), griffithsin (9), MVL (10), and actinohivin (11), are known to bind to the high mannose glycans on gp120, thereby exerting anti-HIV activity. Interestingly, the binding modes and target epitopes on Man-9 are quite distinct for the different lectins. Cyanovirin-N specifically recognizes Man␣(1-2)Man-linked mannose substructures, in particular the D1 and D3 arms of Man-9 (12, 13); DC-SIGN preferentially interacts with the Man␣(1-3)Man␣(1-6)Man trisaccharide (14); griffithsin binds to single mannose units (15); and MVL specifically interacts with the Man␣(1-6)Man␤(1-4)GlcNAc␤(1-4)GlcNAc tetrasaccharide (16). Although no crystal structures for protein-carbohydrate complexes are available for scytovirin and actinohivin, sugar binding studies revealed specificities for Man␣(1-2)Man␣(1-6)Man␣(1-6)Man (17) and Man␣(1-2)Man (18), respectively.Here, we determined the crystal structure of Oscillatoria agardhii agglutinin (OAA), 2 a recently discovered cyanobacterial lectin with potent anti-HIV activity (19); mapped the carbohydrate-binding sites on the protein by NMR spectroscopy; and determined its oligosaccharide specificity. Our results demonstrate that OAA is unique with respect to both its structure and specific carbohydrate binding. Altogether, this work provides the molecular basis for understanding the potent anti-HIV activity of OAA and may aid in its further development as a useful diagnostic and pharmacological re...

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confidence: 99%

Novel Fold and Carbohydrate Specificity of the Potent Anti-HIV Cyanobacterial Lectin from Oscillatoria agardhii

Koharudin

Furey

Gronenborn

2011

Journal of Biological Chemistry

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“…The glycoprotein (GP) on the surface of the Ebola virus has similar N-linked mannose-rich glycans as on the HIV virus, allowing griffithsin to bind GP of the Ebola virus in a similar manner. Thus, griffithsin which possesses good stability over a satisfactory pH and temperature range, can be used as broad spectrum antiviral therapeutic against Ebola infection [63,64]. Smaller griffithsin-derived peptides were also reported to have glycanbinding and HIV-inhibitory properties but have not been evaluated yet as therapeutics against Ebola [65].…”

Section: Human Immunodeficiency Virusmentioning

confidence: 99%

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

Utratna¹,

Deegan²,

Joshi³

2016

J Bioterror Biodef

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Pathogen adherence to a host cell is one of the first essential steps for establishing invasion, colonization and release of virulence factors such as toxins. Understanding the mechanisms used by pathogens and toxins to adhere and invade human cells could lead to the development of new strategies for preventing and controlling the spread of infectious diseases. This review focuses on carbohydrate-lectin interactions utilized by selected biothreat agents to bind and invade host cells. The principle of using anti-adhesion molecules, based on glycobiology research, has already been shown to be effective in the treatment of influenza. Therefore, translating the same principle to other biothreat agents that mediate invasion of a host cell through carbohydrate-lectin mechanisms is a very promising strategy. We investigate recent literature to highlight the latest developments in the field of glycobiology focused on inhibiting the initial steps of pathogen invasion, with examples for bacteria, toxin and virus interactions. The successful glycomimetics and glycoconjugates represent strategies for interruption of adhesion by single molecules and in multivalent systems against uropathogenic E. coli, several toxins (Shiga-like, cholera, botulinum) and wellknown or emerging viruses (influenza, HIV, Ebola, and Zika). This review provides promising directions and prophylactic as well as therapeutic potential of anti-adhesive strategies against selected biothreat targets.

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“…The amino acid sequence of lectin from red marine alga Griffthisia sp. [102] displays sequence similarity with lectin from jack fruit (Artocarpus integrifolia). The common methodology employed to determine the primary structures from red marine alga lectins was a combination of Edman degradation of sets of overlapping peptides and mass spectrometry.…”

Section: Marine Algae Lectinsmentioning

confidence: 99%

Biological Applications of Plants and Algae Lectins: An Overview

Teixeira¹,

Arruda²,

Nascimento³

et al. 2012

Carbohydrates - Comprehensive Studies on Glycobiology and Glycotechnology

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Isolation and Characterization of Griffithsin, a Novel HIV-inactivating Protein, from the Red Alga Griffithsia sp.

Cited by 399 publications

References 45 publications

Novel Fold and Carbohydrate Specificity of the Potent Anti-HIV Cyanobacterial Lectin from Oscillatoria agardhii

Novel Fold and Carbohydrate Specificity of the Potent Anti-HIV Cyanobacterial Lectin from Oscillatoria agardhii

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

Biological Applications of Plants and Algae Lectins: An Overview

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