scholarly journals Molecular Recognition Insights of Sialic Acid Glycans by Distinct Receptors Unveiled by NMR and Molecular Modeling

2021 ◽  
Vol 8 ◽  
Author(s):  
Cátia Oliveira Soares ◽  
Ana Sofia Grosso ◽  
June Ereño-Orbea ◽  
Helena Coelho ◽  
Filipa Marcelo
Keyword(s):  
Sialic Acid ◽  
Molecular Modeling ◽  
Nmr Spectroscopy ◽  
Molecular Recognition ◽  
Complex Structure ◽  
Structural Features ◽  
Sialic Acids ◽  
Infection Process ◽  
Human Cells ◽  
Host Cells

All cells are decorated with a highly dense and complex structure of glycan chains, which are mostly attached to proteins and lipids. In this context, sialic acids are a family of nine-carbon acidic monosaccharides typically found at the terminal position of glycan chains, modulating several physiological and pathological processes. Sialic acids have many structural and modulatory roles due to their negative charge and hydrophilicity. In addition, the recognition of sialic acid glycans by mammalian cell lectins, such as siglecs, has been described as an important immunological checkpoint. Furthermore, sialic acid glycans also play a pivotal role in host–pathogen interactions. Various pathogen receptors exposed on the surface of viruses and bacteria are responsible for the binding to sialic acid sugars located on the surface of host cells, becoming a critical point of contact in the infection process. Understanding the molecular mechanism of sialic acid glycans recognition by sialic acid-binding proteins, present on the surface of pathogens or human cells, is essential to realize the biological mechanism of these events and paves the way for the rational development of strategies to modulate sialic acid-protein interactions in diseases. In this perspective, nuclear magnetic resonance (NMR) spectroscopy, assisted with molecular modeling protocols, is a versatile and powerful technique to investigate the structural and dynamic aspects of glycoconjugates and their interactions in solution at the atomic level. NMR provides the corresponding ligand and protein epitopes, essential for designing and developing potential glycan-based therapies. In this review, we critically discuss the current state of knowledge about the structural features behind the molecular recognition of sialic acid glycans by different receptors, naturally present on human cells or pathogens, disclosed by NMR spectroscopy and molecular modeling protocols.

scholarly journals Molecular recognition of neutral molecules by metalloclefts: synthesis, x-ray structure, proton NMR spectroscopy, electrochemistry, and molecular modeling

1991 ◽  
Vol 56 (7) ◽  
pp. 2371-2380 ◽  
Author(s):  
Arie R. Van Doorn ◽  
Martinus Bos ◽  
Sybolt Harkema ◽  
Johan Van Eerden ◽  
Willem Verboom ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Nmr Spectroscopy ◽  
Molecular Recognition ◽  
Proton Nmr ◽  
Proton Nmr Spectroscopy ◽  
X Ray

scholarly journals Post-Glycosylation Modification of Sialic Acid and Its Role in Virus Pathogenesis

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 171 ◽  
Author(s):  
Park
Keyword(s):  
Sialic Acid ◽  
Mammalian Cells ◽  
Biological Significance ◽  
Extraction Methods ◽  
Sialic Acids ◽  
Neuraminic Acid ◽  
Host Cells ◽  
Viral Receptor ◽  
Site Specific ◽  
Viral Binding

Sialic acids are a family of nine carbon keto-aldononulosonic acids presented at the terminal ends of glycans on cellular membranes. α-Linked sialoglycoconjugates often undergo post-glycosylation modifications, among which O-acetylation of N-acetyl neuraminic acid (Neu5Ac) is the most common in mammalian cells. Isoforms of sialic acid are critical determinants of virus pathogenesis. To date, the focus of viral receptor-mediated attachment has been on Neu5Ac. O-Acetylated Neu5Acs have been largely ignored as receptor determinants of virus pathogenesis, although it is ubiquitous across species. Significantly, the array of structures resulting from site-specific O-acetylation by sialic acid O-acetyltransferases (SOATs) provides a means to examine specificity of viral binding to host cells. Specifically, C4 O-acetylated Neu5Ac can influence virus pathogenicity. However, the biological implications of only O-acetylated Neu5Ac at C7–9 have been explored extensively. This review will highlight the biological significance, extraction methods, and synthetic modifications of C4 O-acetylated Neu5Ac that may provide value in therapeutic developments and targets to prevent virus related diseases.

scholarly journals Single virus assay reveals membrane determinants and mechanistic features of Sendai virus binding

2021 ◽  
Author(s):  
Amy Lam ◽  
Orville O Kirkland ◽  
Papa Freduah Anderson ◽  
Nandini Seetharaman ◽  
Dragan Vujovic ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Lipid Bilayers ◽  
Receptor Binding ◽  
Influenza A ◽  
Viral Vector ◽  
Sendai Virus ◽  
Structural Features ◽  
Host Cells ◽  
Cholesterol Concentration ◽  
Viral Fusion

Sendai virus (SeV, formally murine respirovirus) is a membrane-enveloped, negative sense RNA virus in the Paramyxoviridae family, and is closely related to human parainfluenza viruses. SeV has long been utilized as a model paramyxovirus and has recently gained attention as a viral vector candidate for both laboratory and clinical applications. To infect host cells, SeV must first bind to sialic-acid glycolipid or glycoprotein receptors on the host cell surface via its hemagglutinin-neuraminidase (HN) protein. Receptor binding induces a conformational change in HN, which allosterically triggers the viral fusion (F) protein to catalyze membrane fusion. While it is known that SeV binds to α2,3-linked sialic acid receptors, and there has been some study into the chemical requirements of those receptors, key mechanistic features of SeV binding remain unknown, in part because traditional approaches often convolve binding and fusion. Here, we develop and employ a fluorescence microscopy-based assay to observe SeV binding to supported lipid bilayers (SLBs) at the single particle level, which easily disentangles binding from fusion. Using this assay, we investigate mechanistic questions of SeV binding. We identify chemical structural features of ganglioside receptors that influence viral binding and demonstrate that binding is cooperative with respect to receptor density. We measure the characteristic decay time of unbinding and provide evidence supporting a "rolling" mechanism of viral mobility following receptor binding. We also study the dependence of binding on target cholesterol concentration. Interestingly, we find that while SeV binding shows striking parallels in cooperative binding with a prior report of Influenza A virus, it does not demonstrate a similar sensitivity to cholesterol concentration and receptor nano-cluster formation.

scholarly journals Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein

2021 ◽  
Vol 9 ◽  
Author(s):  
Bingqian Li ◽  
Lin Wang ◽  
Huan Ge ◽  
Xianglei Zhang ◽  
Penxuan Ren ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Binding Sites ◽  
Sialic Acids ◽  
Host Cells ◽  
Spike Protein ◽  
Molecular Probe ◽  
Acetylneuraminic Acid ◽  
Mass Spectrum Analysis ◽  
Multiple Receptors ◽  
Potential Binding

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.

Structural studies on the interaction of saccharides and glycomimetics with galectin-1: A 3D perspective using a combined molecular modeling and NMR approach

2011 ◽  
Vol 84 (1) ◽  
pp. 49-64 ◽  
Author(s):  
Sonsoles Martín-Santamaría ◽  
Hans-Joachim Gabius ◽  
Jesús Jiménez-Barbero
Keyword(s):  
Molecular Modeling ◽  
Nmr Spectroscopy ◽  
Structural Features ◽  
Structural Studies ◽  
Lectin Receptors ◽  
Recognition Process

The interaction of a variety of saccharides and mimetics thereof with lectin receptors has been studied using a combination of molecular modeling protocols and NMR spectroscopy techniques. It is shown that both methods complement each other in a synergistic manner to provide a detailed perspective of the conformational and structural features of the recognition process.

COMPARATIVE ACTION OF VARIOUS OESTROGENIC COMPOUNDS ON MOUSE VAGINAL SIALIC ACIDS (II)

1969 ◽  
Vol 62 (4) ◽  
pp. 663-670 ◽  
Author(s):  
Lars Carlborg
Keyword(s):  
Sialic Acid ◽  
Response Curve ◽  
Sialic Acids ◽  
Clear Cut ◽  
Suitable Parameter ◽  
Sufficient Degree ◽  
Comparative Action ◽  
Relative Potencies ◽  
Good Agreement

ABSTRACT Oestrogens administered in lower doses than necessary to induce full cornification of the mouse vagina induce mucification. It was shown previously that the degree of mucification could be estimated by quantitative determination of sialic acids. A suitable parameter for oestrogen assay was the measurement of vaginal sialic acid concentration which exhibited a clear cut dose response curve. Eleven assays of various oestrogens were performed with this method. Their estimated relative potencies were in good agreement with other routine oestrogen assays. A statistically sufficient degree of precision was found. The sensitivity was of the same order, or slightly higher, than the Allen-Doisy test.

Interspecific variation of zona pellucida glycoconjugates in several species of marsupial

Reproduction ◽  
2000 ◽  
pp. 111-120 ◽  
Author(s):  
JA Chapman ◽  
OW Wiebkin ◽  
WG Breed
Keyword(s):  
Glycine Max ◽  
Sialic Acid ◽  
Zona Pellucida ◽  
Fluorescein Isothiocyanate ◽  
Interspecific Variation ◽  
Lectin Histochemistry ◽  
Sialic Acids ◽  
Arachis Hypogea ◽  
Marsupial Species ◽  
Similar Intensity

The zona pellucida glycoconjugate content of several marsupial species was investigated using differential lectin histochemistry. Ovaries from fat-tailed dunnarts, a southern brown bandicoot, grey short-tailed opossums, brushtail possums, ringtail possums, koalas and eastern grey kangaroos were fixed, embedded in paraffin wax, sectioned and stained with ten fluorescein isothiocyanate-conjugated lectins. Sections were also incubated with either neuraminidase or saponified, respectively, before incubation with the lectins to identify saccharide residues masked by sialic acids or O-acetyl groups on sialic acids. The zonae pellucidae surrounding the oocytes of the marsupials demonstrated interspecific variation in glycoconjugate content, with mannose-containing glycoconjugates exhibiting the greatest variation. Some of the zona pellucida glycoconjugates of all species, except those of the opossums, were masked by sialic acid with an increase in fluorescence with lectins from Arachis hypogea (PNA), and Glycine max (SBA), after desialylation. The disaccharide beta-galactose(1-4)N-acetyl-D-glucosamine appeared to be conformationally masked by O-acetyl groups of sialic acids in the zonae pellucidae of all species, with an increase in fluorescence with the lectin from Erythrina cristagalli (ECA), after saponification. Similar intensity and localization of beta-(1-4)-N-acetyl-D-glucosamine, as shown by staining of the lectin from Triticum vulgaris (WGA), to the inner and outer regions of the zona pellucida, were found to those reported in eutherian species. WGA fluorescence became uniform throughout the zonae pellucidae after saponification, indicating differential O-acetylation of sialic acids on the internal compartment of the zonae pellucidae.

scholarly journals Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces

2021 ◽  
Author(s):  
Yixuan Xie ◽  
Siyu Chen ◽  
Qiongyu Li ◽  
Ying Sheng ◽  
Michael R Alvarez ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Sialic Acid ◽  
Membrane Proteins ◽  
Cell Membranes ◽  
Sialic Acids ◽  
Cross Linking ◽  
Protein Networks ◽  
Cell Surfaces ◽  
Protein Cross Linking

A cross-linking method is developed to elucidate the glycan-mediated interactions between membrane proteins through sialic acids. The method provides previously unknown extensive glycomic interactions on cell membranes. The vast majority...

scholarly journals Three-Dimensional Structures of Carbohydrates and Where to Find Them

2020 ◽  
Vol 21 (20) ◽  
pp. 7702 ◽  
Author(s):  
Sofya I. Scherbinina ◽  
Philip V. Toukach
Keyword(s):  
Experimental Data ◽  
Molecular Modeling ◽  
Computational Methods ◽  
Three Dimensional ◽  
Structural Diversity ◽  
Structural Data ◽  
Structural Features ◽  
Data Validation ◽  
Data Generation ◽  
Efficient Treatment

Analysis and systematization of accumulated data on carbohydrate structural diversity is a subject of great interest for structural glycobiology. Despite being a challenging task, development of computational methods for efficient treatment and management of spatial (3D) structural features of carbohydrates breaks new ground in modern glycoscience. This review is dedicated to approaches of chemo- and glyco-informatics towards 3D structural data generation, deposition and processing in regard to carbohydrates and their derivatives. Databases, molecular modeling and experimental data validation services, and structure visualization facilities developed for last five years are reviewed.

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