Topology of Glycosylation — a Histochemist's View

Pavelka, Margit

doi:10.1002/9783527614738.ch6

Cited by 12 publications

(10 citation statements)

References 56 publications

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“…In the endoplasmic reticulum, the en bloc transfer from the dolichol precursor to the protein takes place followed by the first steps of modification, before any trimmed N-glycan moves to the cis-Golgi. Within the Golgi network further modification to the complex-type Nglycans takes place, and sialylation as the final modification occurs by the corresponding sialyltransferases in the trans-Golgi [288][289][290][291][292]. The complexity of the enzymatic reactions and the topological order of the enzymes involved along the route of a glycoprotein's The two types of ubiquitous enzymatic sialylation may even occur on different antennae in one glycan.…”

Section: Review Articlementioning

confidence: 97%

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Reuter¹,

Gabius²

1999

Cellular and Molecular Life Sciences (CMLS)

214

141

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Protein and lipid glycosylation is a ubiquitous phenomenon. The task of cataloguing the great structural variety of the glycan part has demanded considerable efforts over decades. This patient endeavor was imperative to discern the inherent rules of glycosylation which cannot affirm assumptions on a purely coincidental nature of this type of protein and lipid modification. These results together with theoretical considerations uncover a salient property of oligosaccharides. In comparison with amino acids and nucleotides, monosaccharides excel in their potential to serve as units of hardware for storing biological information. Thus, the view that glycan chains exclusively affect physiochemical properties of the conjugates is indubitably flawed. This original concept has been decisively jolted by the discovery of endogenous receptors (lectins) for distinct glycan epitopes which are as characteristic as a fingerprint or a signature for a certain protein (class) or cell type. Recent evidence documents that these binding proteins are even endowed with the capacity to select distinct low-energy conformers of the often rather flexible oligosaccharides, granting entry to a new level of regulation of ligand affinity by shifting conformer equilibria. The assessment of the details of this recognition by X-ray crystallography, nuclear magnetic resonance spectroscopy, microcalorimetry and custom-made derivatives is supposed to justify a guarded optimism in satisfying the need for innovative drug design in antiadhesion therapy, for example against viral or bacterial infections and unwanted inflammation. This review presents a survey of the structural aspects of glycosylation and of evidence to poignantly endorse the notion that carrier-attached glycan chains can partake in biological information transfer at the level of cell compartments, cells and organs.

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Section: Review Articlementioning

confidence: 97%

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Reuter¹,

Gabius²

1999

Cellular and Molecular Life Sciences (CMLS)

214

141

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“…This staggering number is a strong argument in favor of a possible role of carbohydrate structures in information storage and transfer. Since the display of glycosyltransferases in the Golgi region and the availability of activated substrates for chain elongation can modulate the synthesis and structural aspects of oligosaccharides (Brockhausen and Schachter 1997;Pavelka 1997;Varki 1998), this code system can readily take modulatory influences into account. Although gene expression for glycosyltransferases determines the display of enzyme molecules, their topological arrangement is subject to variations, conferring flexibility to product generation even without any alteration in the extent of gene expression.…”

Section: Animal Lectins and The Sugar Codementioning

confidence: 99%

The application of thermodynamic principles to histochemical and morphometric tissue research: principles and practical outline with focus on the glycosciences

Kayser

Gabius

1999

Cell and Tissue Research

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Physicochemical terms such as entropy or current of entropy are commonly used to refer solely to the description of reactions in the realm of chemistry and physics. Since these thermodynamic terms have a predictive value for the further course of development of such reactions, e.g., extent of a chemical reaction or affinity of molecular interactions, it is tempting to introduce the respective algorithms to biological problems. By combining quantitative morphology with the histochemical visualization of distinct cellular and textural properties such as nuclear DNA contents or intensity of histochemical staining, equations from the general theory of thermodynamics can be adapted. They permit appropriate calculations to be performed which introduce the entropy concept to the processing of the information collected by analysis of structures formed by histochemically labeling cells. The theory of weighted graphs offers the appropriate mathematical tools. Nuclei are defined as vertices. Their DNA contents measured by the integrated optical density or additional cellular features (for example staining intensity of applied immuno-/ligandohistochemical probes) define the associated weights and the minimum spanning tree as a derivative from Voronoi's theorem for the definition of the geometrical neighborhood. This technique is equivalent to syntactic structure analysis as developed by Lu and Fu (1978), Sanfeliu et al. (1981), Kayser and Schlegel (1982), and Kayser (1988). Assuming that the texture of a healthy tissue is displayed in the energetically most efficient and stable manner to perform the required biological functions, i.e., to maintain the lowest level of entropy, deviations from this level are reflected in differences in distances and weights between neighboring nuclei or cells. The measure of textural differences in relation to the normal appearance of an organ or tissue is denoted as structural entropy. Since organisms or their compartments are thermodynamically open systems, they are insufficiently described by the (structural) entropy. This parameter only provides a snapshot, with no information about the status of entropy changes from a directed exchange with the environment. The current of entropy, which is equivalent to the amount of entropy exported or imported through a boundary, is an appropriate measure of the "thermodynamic distance" of the system under consideration from its environment, as is readily appreciated for tumors. A solid tumor is a biological system embedded in another one (healthy tissue). Its current of entropy can be calculated if its boundary and proliferative activity are known. This parameter can be measured by histochemical methods (Ki-67 antibody) or from the cytometric characteristics (percentage of S-phase-related tumor cells), and the boundary can be measured by the volume fraction of the internal vessels and the size of the external surface of the tumor. Since biochemical factors will contribute to the generation and establishment of these structural and thermodynamic feature...

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“…Intercellular and temporal flexibility turns the available letter repertoire into an array of alternative structures (biosignals). Indeed, the observations that the profile of glycans is not genetically strictly coded but influenced by the presence and relative positioning of the set of enzymes in the assembly line and the actual availability of activated substrates such as nucleotide donors argues in favor of purpose versus randomness (Abeijon et al, 1997;Pavelka, 1997;Varki, 1998). Thus, the prerequisite for rapid and multifarious modulation mentioned in the introductory paragraph is adequately fulfilled in the sugar code.…”

Section: The Sugar Code: Basic Principlesmentioning

confidence: 90%

Biological Information Transfer Beyond the Genetic Code: The Sugar Code

Gabius

2008

Biosemiotics

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In the era of genetic engineering, cloning, and genome sequencing, the focus of research on the genetic code has received an even further accentuation in the public eye. When, however, aspiring to understand intra-and intercellular recognition processes comprehensively, the two biochemical dimensions established by nucleic acids and proteins are not sufficient to satisfactorily explain all molecular events in, e.g. cell adhesion or routing. To bridge this gap consideration of further code systems is essential. A third biochemical alphabet forming code words with an information storage capacity second to no other substance class in rather small units (words, sentences) is established by monosaccharides (letters). As hardware oligosaccharides surpass peptides by more than seven orders of magnitude in the theoretical ability to build isomers, then the total of conceivable hexamers is calculated. Beyond the sequence complexity application of nuclear magnetic resonance (NMR) spectroscopy and molecular modeling have been instrumental to discover that even small glycans can often reside in not only one but several distinct low-energy conformations (keys). Intriguingly, conformers can display notably different capacities to fit snugly into the binding site of nonhomologous receptors (locks). This process, experimentally verified for two classes of lectins, is termed "differential conformer selection." It adds potential for shifts of the conformer equilibrium to modulate ligand properties dynamically and reversibly to the wellknown changes of sequence (including anomeric positioning and linkage points) and of pattern of substitution, e.g. by sulfation. In the intimate interplay with sugar receptors (lectins, enzymes, and antibodies) the message of coding units of the sugar code is deciphered. This communication will trigger postbinding signaling and the intended biological response. Knowledge about the driving forces for the molecular rendezvous, that is, contributions of bidentate or cooperative hydrogen bonds, dispersion forces, stacking and solvent rearrangement, will enable the design * Reprinted with permission from Naturwissenschaften, Vol. 87 (2000), pp. 108-121. Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstr. 13, D-80539 München, Germany, e-mail: gabius@tiph.vetmed.uni-muenchen

show abstract

Topology of Glycosylation — a Histochemist's View

Cited by 12 publications

References 56 publications

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Eukaryotic glycosylation: whim of nature or multipurpose tool?

The application of thermodynamic principles to histochemical and morphometric tissue research: principles and practical outline with focus on the glycosciences

Biological Information Transfer Beyond the Genetic Code: The Sugar Code

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