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Transforming Growth Factor-α and Epidermal Growth Factor
Published in Jason Kelley, Cytokines of the Lung, 2022
Glycosylation studies of the receptor indicate the presence of 10 or 11 N-linked oligosaccharides, situated on the extracellular portion of the molecule (Mayes and Waterfield, 1984; Soderquist and Carpenter, 1984). The N-linked glycosylation of the receptor is essential for translocation of the receptor to the cell surface, EGF binding to the receptor, and receptor phosphorylation after ligand binding (Soderquist and Carpenter, 1984). These observations suggest that the cotranslational addition of N-linked oligosaccharides contributes to a functional conformation of the receptor.
Enzymatic Degradation of Bradykinin
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Randal A. Skidgel, Ervin G. Erdös
Aminopeptidase P is membrane-bound via a glycosylphosphatidylinositol (GPI) anchor and can be solubilized with phosphatidylinositol-specific phospholipase C (PI-PLC) (Hooper and Turner, 1988; Hooper et al., 1990; Simmons and Orawski, 1992; Orawski and Simmons, 1995). Under denaturing conditions in SDS-PAGE, the enzyme, as a single-chain protein, has Mr = 90,000—95,000 and contains about 17–25% carbohydrate by weight (Hooper et al., 1990; Simmons and Orawski, 1992; Orawski and Simmons, 1995). There are six consensus N-linked glycosylation sequences, all of which are coupled to carbohydrates in the N-terminal half of the protein (Vergas Romero et al., 1995). After gel filtration chromatography, the purified enzyme has a multimeric structure with a molecular mass of 220—360 kDa (Hooper et al., 1990; Simmons and Orawski, 1992; Orawski and Simmons, 1995), which varies depending on the salt concentration (Orawski and Simmons, 1995). Partial protein sequencing of aminopeptidase P, purified from guinea pig lung and kidney (Denslow et al., 1994), and the full sequence of the pig kidney enzyme (Vergas Romero et al., 1995) show that aminopeptidase P has some sequence similarity to human and E. coli prolidase as well as to E. coli aminopeptidase P, belonging to a newly recognized family of proline peptidases.
Intracellular Maturation of Acute Phase Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Erik Fries, E. Mathilda Sjöberg
Oligosaccharides may also be linked to proteins via an oxygen atom of a serine or threonine residue. However, this is a relatively rare modification.74,75 It is possible that the scarcity of examples is a reflection of the fact that O-linked oligosaccharides are relatively difficult to detect. In contrast to N-linked glycosylation, the potential sites for 0-linked glycosylation cannot be predicted from amino acid sequence.75 Furthermore, since O-linked sugars are often small, their (enzymatic)76 removal may not lead to a noticeable shift in the electrophoretic mobility of a protein. A lectin which binds oligopeptides with 0-linked sugars should be useful in the detection of this modification.77
Impact of IgG subclass on monoclonal antibody developability
Published in mAbs, 2023
Paul Cain, Lihua Huang, Yu Tang, Victor Anguiano, Yiqing Feng
N-linked glycosylation at N297 in the Fc domain is a common feature in all naturally occurring mAbs. While numerous reports have studied glycosylation differences among the subclasses for endogenous IgGs and the implications to the health of the plasma donors,31,32 scant literature exists detailing the influence of IgG subclass on glycan structure from recombinantly produced mAbs.33 Given the importance of glycan structure, namely the impact of afucosylation and galactosylation, for effector functions, the literature on glycan content for recombinant mAbs has primarily focussed on IgG1.34 The Fc mutation F241A in an IgG1 mAb has been shown to alter glycan structures, consequently modulating effector functions.35,36 In addition to revealing the impact of Fc-galactosylation on effector functions, Aoyama et al.36 demonstrated that an G1F isomer, designated G1aF, and G2F have a stabilizing effect on the CH2 domain compared to G0F and the other G1F isomer, G1bF. In this work, we found an IgG subclass-dependent trend that the IgG4PAA mAbs tend to have higher level of G0F, whereas IgG1 and IgG1EN mAbs showed comparatively higher level of G1F across each series, without influence from the variable region. The potential implication of the Fc-glycosylation content difference on physicochemical stability was not further investigated.
Searching for glycomic biomarkers for predicting resilience and vulnerability in a rat model of posttraumatic stress disorder
Published in Stress, 2020
Csilla Lea Fazekas, Eszter Sipos, Thomas Klaric, Bibiána Török, Manon Bellardie, Gordana Nedic Erjave, Matea Nikolac Perkovic, Gordan Lauc, Nela Pivac, Dóra Zelena
Glycans are enzymatic post-translational modificators of proteins and lipids (Ohtsubo & Marth, 2006). N-linked glycosylation is the most common type (Pivac et al., 2011) and it can modulate the function of a protein to be able to adapt to the constantly changing environment (Lauc et al., 2016). Dysregulation of glycosylation is associated with a wide range of diseases, including cancer, diabetes, cardiovascular and immunological disorders (Ohtsubo & Marth, 2006). About 80% of the glycosylation-related disorders affect the nervous system, providing a plausible and comprehensive explanation for the diverse pathomechanisms. It might be explained by the existence of the perineuronal net composed of glycans, serving as a regulatory factor for interneuronal communication (Wen et al., 2018). Recent technological advances allow reliable, high-throughput quantification of glycans (Pivac et al., 2011). In relation to psychiatric disorders, changes in glycan-related processes were found in attention deficit hyperactivity disorder (ADHD) (Pivac et al., 2011), Alzheimer’s disease, Parkinson’s disease (Shi et al., 2013), autism and schizophrenia (Barone et al., 2012). However, glycan alterations in relation to PTSD were not extensively studied so far. A small case report failed to find alteration (Moreno-Villanueva et al., 2013), while our recent human study on 543 male war veterans found 6 plasma N-glycans to be associated with PTSD (Tudor et al., 2019). There is no information on glycosylation patterns in animal models of PTSD, however, there are few studies on stressed animals (Konjevod et al., 2019).
Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Anna Di Fiore, Claudiu T. Supuran, Andrea Scaloni, Giuseppina De Simone
N-linked glycosylation is an enzyme-catalysed process involving the attachment of an oligosaccharide (also referred to as glycan) to the amide nitrogen of protein N residues89. The attachment of the glycan chain to the protein requires the enzymatic recognition of a consensus N-X-S/T sequence. In eukaryotes, the biosynthesis of N-linked glycoproteins starts in the ER, continues in the Golgi and ends at the plasma membrane, where they are either secreted or become embedded in the plasma membrane. The nature of the attached N-linked glycans is determined by the protein and the cell in which it is expressed. Depending on the nature of the various monosaccharides adducted at the common N-linked pentasaccharide (mannose3N-acetylglucosamine2 - Man3GlcNAc2), different oligomannose, complex, and hybrid structures occur in glycoproteins. These structures mediate many protein properties, such as corresponding conformation, folding, solubility and antigenicity as well as cell-matrix and cell-cell interactions90. Because of their impact in various biological processes, protein N-linked glycans can be used as a diagnostic marker for the diagnosis and monitoring of various chronic diseases and cancers.