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Journal ArticleDOI

On the structural significance of the linkage region constituents of N-glycoproteins: an X-ray crystallographic investigation using models and analogs.

TL;DR: It is speculated that the linkage region constituents of the eukaryotic N-glycoproteins appear to fulfill three essential structural requirements: rigidity, planarity, and linearity and these are met by the trisaccharide core and Asn at the linkage area.
About: This article is published in Biochemical and Biophysical Research Communications.The article was published on 2003-12-12. It has received 20 citations till now.
Citations
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Journal ArticleDOI
TL;DR: This review provides a didactic step-by-step survey of the concept of the sugar code and the way strategic combination of experimental approaches characterizes structure-function relationships, with resources for teaching.

188 citations

Journal ArticleDOI
TL;DR: The article summarizes the information that is gained from and the errors that are found in carbohydrate structures in the Protein Data Bank.
Abstract: Knowledge of the three-dimensional structures of the carbo­hydrate molecules is indispensable for a full understanding of the molecular processes in which carbohydrates are involved, such as protein glycosylation or protein–carbohydrate interactions. The Protein Data Bank (PDB) is a valuable resource for three-dimensional structural information on glycoproteins and protein–carbohydrate complexes. Unfortunately, many carbohydrate moieties in the PDB contain inconsistencies or errors. This article gives an overview of the information that can be obtained from individual PDB entries and from statistical analyses of sets of three-dimensional structures, of typical problems that arise during the analysis of carbohydrate three-dimensional structures and of the validation tools that are currently available to scientists to evaluate the quality of these structures.

63 citations


Cites result from "On the structural significance of t..."

  • ...These results correspond well to the values measured from small-molecule crystal structures of analogues of this linkage (Lakshmanan et al., 2003)....

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Journal ArticleDOI
TL;DR: An analysis of C-H)...O interactions in the crystal structures of all N-glycoprotein linkage region models and analogs reveals a cooperative network of bifurcated hydrogen bonds consisting of N-H...O and C-h...O interactions seen uniquely for the models.
Abstract: Elucidation of the intra- and intermolecular carbohydrate-protein interactions would greatly contribute toward obtaining a better understanding of the structure-function correlations of the protein-linked glycans. The weak interactions involving C-H...O have recently been attracting immense attention in the domain of biomolecular recognition. However, there has been no report so far on the occurrence of C-H...O hydrogen bonds in the crystal structures of models and analogs of N-glycoproteins. We present herein an analysis of C-H...O interactions in the crystal structures of all N-glycoprotein linkage region models and analogs. The study reveals a cooperative network of bifurcated hydrogen bonds consisting of N-H...O and C-H...O interactions seen uniquely for the models. The cooperative network consists of two antiparallel chains of bifurcated hydrogen bonds, one involving N1-H, C2'-H and O1' of the aglycon moiety and the other involving N2-H, C1-H and O1'' of the sugar. Such bifurcated hydrogen bonds between the core glycan and protein are likely to play an important role in the folding and stabilization of proteins.

28 citations


Cites background from "On the structural significance of t..."

  • ...Our recent crystallographic examination (Lakshmanan et al., 2003) of several β-1-N-acylamidoglycopyranose derivatives demonstrated, for the first time, the effect of structural variation in both the linkage region sugar and its aglycon moiety on the N-glycosidic torsion....

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  • ..., 2003), and GlcNAcβNHPr (12) (Lakshmanan et al., 2003) are analogs of the respective sugar conjugates of Gln, hitherto unknown in nature....

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  • ..., 1997) and RhaβNHAc (6) (Lakshmanan et al., 2003) are models of GlcβAsn and RhaβAsn, respectively, of the unusual N-glycosidic linkages found in Halobacter halobium S layer glycoprotein and surface layer glycoprotein of Bacillus stearothermophillus, while LacβNHAc....

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  • ...The propionamido derivatives, GlcβNHPr (11) (Lakshmanan et al., 2003), and GlcNAcβNHPr (12) (Lakshmanan et al....

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  • ...…1982; Sriram et al., 1997; Sriram D, Lakshmanan T et al., 1998; Sriram D, Srinivasan S et al., 1998; Lakshmanan and Loganathan, 2001; Aich et al., Dedicated to late Prof. George Alan Jeffrey 1To whom correspondence should be addressed; e-mail: loganath@iitm.ac.in 2003; Lakshmanan et al., 2003)....

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Journal ArticleDOI
TL;DR: The authors suggested the occurrence of two conformations for the O-GlcNAc-Ser glycosidic linkage, each displaying similar occupancy, and this experimental finding clearly suggests a significant degree of mobility for this moiety.
Abstract: There is an increasing interest in clarifying the role of bN-acetyl-d-glucosamine (b-GlcNAc) since the discovery that it modifies the chemical, biochemical, and biomedical behavior of an increasing number of cytoplasmic and nuclear proteins, such as transcription factors, nuclear pore proteins, oncogene products, tumor suppressors, and cytoskeletal proteins. This post-translational glycosylation is highly dynamic and draws comparisons with protein phosphorylation as a biological control mechanism. It has been implicated in gene transcription, nuclear trafficking, protein translation, signal transduction, regulation of protein–protein interactions, and the sensing of nutritional levels within the cell. Furthermore, there is clear evidence that the aberrant OGlcNAc modification of proteins is correlated with diabetes, tumorgenesis, and even with Alzheimer s disease. From a structural point of view, O-GlcNAc glycosylation sites do not show obvious consensus sequences. Additionally, in contrast to classical protein glycosylation, O-GlcNAc is not elongated or further modified with a complex array of glycans. However, in spite of the importance of O-GlcNAc glycosylation, sparse information has been reported to date concerning the geometry and dynamics of b-O-GlcNAc-Ser and b-O-GlcNAc-Thr motifs. On the contrary, significant progress has been made with regard to the understanding of the structural properties of the b-N-GlcNAc-Asn fragment. In fact, while numerous crystal structures containing this fragment have been reported to date, only one crystal structure with a serine residue glycosylated with a b-O-GlcNAc has been deposited in the Protein Data Bank. This crystal structure shows the complex between a b-O-GlcNAc glycopeptide with the sequence FAPSNYPAL (named K3G) and the MHC Class 1 H-2D antibody. The authors suggested the occurrence of two conformations for the O-GlcNAc-Ser glycosidic linkage, each displaying similar occupancy. This experimental finding clearly suggests a significant degree of mobility for this moiety. One of these conformers is shown in Figure 1. On the other hand, the conformational study in aqueous solution of glycopeptides containing the b-O-GlcNAc-Ser/

25 citations

Journal ArticleDOI
TL;DR: Qualitative and quantitative analyses offer a global picture of carbohydrate structural content on PDB, potentially supporting the building of new models for carbohydrate related biological phenomena at the atomistic level, including new developments on force field parameters.
Abstract: Carbohydrates are well known for their physicochemical, biological, functional, and therapeutic characteristics. Unfortunately, their chemical nature imposes severe challenges for the structural elucidation of these phenomena, impairing not only the depth of our understanding of carbohydrates but also the development of new biotechnological and therapeutic applications based on these molecules. In the recent past, the amount of structural information, obtained mainly from X-ray crystallography, has increased progressively, as well as its quality. In this context, the current work presents a global analysis of the carbohydrate information available in the Protein Data Bank (PDB). From high quality structures, it is clear that most of the data are highly concentrated on a few sets of residue types, on their monosaccharidic forms, and connected by a small diversity of glycosidic linkages. The geometries of these linkages can be mostly associated with the types of linkages instead of residues, while the level of puckering distortion was characterized, quantified, and located in a pseudorotational equilibrium landscape, not only to local minima but also to transitional states. These qualitative and quantitative analyses offer a global picture of the carbohydrate structural content in the PDB, potentially supporting the building of new models for carbohydrate-related biological phenomena at the atomistic level, including new developments on force field parameters.

21 citations

References
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Journal ArticleDOI
TL;DR: The structure of ASPARAGINE-LINKed OLIGOSACCI-IARIDES and transfer-Oligosaccharide Structural Requirements, and Sequence of Processing and Specificity of Processing Enzymes are presented.
Abstract: PERSPECTIVES AND SUMMARY 631 STRUCTURES OF ASPARAGINE-LINKED OLIGOSACCI-IARIDES 632 ASSEMBLY AND TRANSFER OF THE LIPID-LINKED OLIGOSACCHARIDE ...... 635 Assembly 635 Transfer-Oligosaccharide Structural Requirements 636 Transfer-Role of Peptide Acceptor 637 OLIGOSACCHARIDE P OCESSING 639 Sequence of Processing 639 Subcellular Localization of Processing Enzymes 641 Processing in Lower Organisms 643 Specificity of Processing Enzymes 644 OTHER POS’VI~RANSLATIONAL MODIFICATIONS 653 CONTROL F OLIGOSACCHARIDE PROCESSING 655

4,699 citations

Journal ArticleDOI
TL;DR: The aim of this review is to describe the glycopeptide linkages that have been found to date and specify their presence on well-characterized glycoproteins and with a number of human disease states in which defects in enzymatic transfer of saccharides to protein have been implicated.
Abstract: Formation of the sugar-amino acid linkage is a crucial event in the biosynthesis of the carbohydrate units of glycoproteins. It sets into motion a complex series of posttranslational enzymatic steps that lead to the formation of a host of protein-bound oligosaccharides with diverse biological functions. These reactions occur throughout the entire phylogenetic spectrum, ranging from archaea and eubacteria to eukaryotes. It is the aim of this review to describe the glycopeptide linkages that have been found to date and specify their presence on well-characterized glycoproteins. A survey is also made of the enzymes involved in the formation of the various glycopeptide bonds as well as the site of their intracellular action and their affinity for particular peptide domains is evaluated. This examination indicates that 13 different monosaccharides and 8 amino acids are involved in glycoprotein linkages leading to a total of at least 41 bonds, if the anomeric configurations, the phosphoglycosyl linkages, as well as the GPI (glycophosphatidylinositol) phosphoethanolamine bridge are also considered. These bonds represent the products of N- and O-glycosylation, C-mannosylation, phosphoglycation, and glypiation. Currently at least 16 enzymes involved in their formation have been identified and in many cases cloned. Their intracellular site of action varies and includes the endoplasmic reticulum, Golgi apparatus, cytosol, and nucleus. With the exception of the Asn-linked carbohydrate and the GPI anchor, which are transferred to the polypeptide en bloc, the sugar-amino acid linkages are formed by the enzymatic transfer of an activated monosaccharide directly to the protein. This review also deals briefly with glycosidases, which are involved in physiologically important cleavages of glycopeptide bonds in higher organisms, and with a number of human disease states in which defects in enzymatic transfer of saccharides to protein have been implicated.

1,309 citations

Journal ArticleDOI
TL;DR: Examples are given of changes that occur in the carbohydrates of soluble and cell-surface glycoproteins during differentiation, growth and malignancy, which further highlight the important role of these substances in health and disease.
Abstract: During the last decade, there have been enormous advances in our knowledge of glycoproteins and the stage has been set for the biotechnological production of many of them for therapeutic use. These advances are reviewed, with special emphasis on the structure and function of the glycoproteins (excluding the proteoglycans). Current methods for structural analysis of glycoproteins are surveyed, as are novel carbohydrate-peptide linking groups, and mono- and oligo-saccharide constituents found in these macromolecules. The possible roles of the carbohydrate units in modulating the physicochemical and biological properties of the parent proteins are discussed, and evidence is presented on their roles as recognition determinants between molecules and cells, or cell and cells. Finally, examples are given of changes that occur in the carbohydrates of soluble and cell-surface glycoproteins during differentiation, growth and malignancy, which further highlight the important role of these substances in health and disease.

803 citations

Journal ArticleDOI
Akira Kobata1
TL;DR: In this article, a review of the analytical techniques for the structural study of the sugar chains of glycoproteins, the structural characteristics of sugar chains and the biosynthetic mechanism to produce such characteristics.
Abstract: Most proteins within living organisms contain sugar chains. Recent advancements in cell biology have revealed that many of these sugar chains play important roles as signals for cell-surface recognition phenomena in multi-cellular organisms. In order to elucidate the biological information included in the sugar chains and link them with biology, a novel scientific field called 'glycobiology' has been established. This review will give an outline of the analytical techniques for the structural study of the sugar chains of glycoproteins, the structural characteristics of the sugar chains and the biosynthetic mechanism to produce such characteristics. Based on this knowledge, functional aspects of the sugar chains of glycohormones and of those in the immune system will be described to help others understand this new scientific field.

384 citations