Unusual glycosylation of proteins: Beyond the universal sequon and other amino acids

Dutta, Devawati; Mandal, Chhabinath; Mandal, Chitra

doi:10.1016/j.bbagen.2017.08.025

Cited by 36 publications

(29 citation statements)

References 138 publications

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“…It has been reported that there is complete modification of every Glu residue to Gla in the Gla domain of serum-derived Factor IX [2]. However, we observed one tryptic peptide from the Gla domain, T 38 [18][19][20] and Asp64 undergoes partial β-hydroxylation (26-33%) [16,19]. Consistent with this, PSMs containing the two O-linked sites were not observed while the tryptic peptide D 64 DINSYECWPFGFEGK 80 containing Asp64 was observed in an unmodified form.…”

Section: High Sequence Coverage Obtained Of Factor IX Using Proteomicmentioning

confidence: 57%

“…The occupancy of the N-linked site was approximately 1.4%. The attachment of N-glycans in non-consensus motifs, although rare, has been previously documented [38], including in the heavy chain and serine protease domain of Factor XI and protein C, respectively [39,40]. The addition of "′" in the annotated ETciD spectra represents even-electron z-ions [37].…”

Section: O-glycan Monosaccharide Compositions and Occupancy At Ser141mentioning

confidence: 99%

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Identification of novel glycosylation events on human serum-derived Factor IX

Pegg

Zacchi

Recinos

et al. 2019

Preprint

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ABSTRACTHuman Factor IX is a highly post-translationally modified protein that is an important clotting factor in the blood coagulation cascade. Functional deficiencies in Factor IX result in the bleeding disorder haemophilia B, which is treated with plasma-derived or recombinant Factor IX concentrates. Here, we investigated the post-translational modifications of human serum-derived Factor IX and report previously undescribed O-linked monosaccharide compositions at serine 141 and a novel site of glycosylation. At serine 141 we observed two monosaccharide compositions, with HexNAc1Hex1NeuAc2 dominant and a low level of HexNAc1Hex1NeuAc1. This O-linked site lies N-terminal to the first cleavage site for the activation peptide, an important region of the protein that is removed to activate Factor IX. The novel site is an N-linked site in the serine protease domain with low occupancy in a non-canonical consensus motif at asparagine 258, observed with a HexNAc4Hex5NeuAc2 monosaccharide composition attached. This is the first reported instance of a site of modification in the serine protease domain. The description of these glycosylation events provides a basis for future functional studies and contributes to structural characterisation of native Factor IX for the production of effective therapeutic biosimilars and biobetters.

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Section: High Sequence Coverage Obtained Of Factor IX Using Proteomicmentioning

confidence: 57%

Section: O-glycan Monosaccharide Compositions and Occupancy At Ser141mentioning

confidence: 99%

Identification of novel glycosylation events on human serum-derived Factor IX

Pegg

Zacchi

Recinos

et al. 2019

Preprint

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“…Aberrant glycosylation represents a potential hallmark of oncogenesis [ 46 , 47 ]. These alterations consist in (a) changes in the amount, linkage, and acetylation of sialic acids; (b) modification of proteins by the monosaccharide N -acetylglucosamine ( O -GlcNAcylation); (c) alterations in sulfation of glycosaminoglycans; and (d) modulation of the enzymes that attach glycosylphosphatidylinositol (GPI) anchors to proteins [ 48 – 50 ]. The enzymes responsible for these alterations are regulated by oncogenic growth factor signaling and represent novel therapeutic targets for cancer diagnostic and therapeutic strategies, such as the development of glycosyltransferase inhibitors, glycomimetics, and glycan/glycopeptide-based vaccines [ 51 ].…”

Section: Metabolism: a Long-standing Hallmark Of The Cancer Cellmentioning

confidence: 99%

Metabolic Footprints and Molecular Subtypes in Breast Cancer

et al. 2017

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Cancer treatment options are increasing. However, even among the same tumor histotype, interpatient tumor heterogeneity should be considered for best therapeutic result. Metabolomics represents the last addition to promising “omic” sciences such as genomics, transcriptomics, and proteomics. Biochemical transformation processes underlying energy production and biosynthetic processes have been recognized as a hallmark of the cancer cell and hold a promise to build a bridge between genotype and phenotype. Since breast tumors represent a collection of different diseases, understanding metabolic differences between molecular subtypes offers a way to identify new subtype-specific treatment strategies, especially if metabolite changes are evaluated in the broader context of the network of enzymatic reactions and pathways. Here, after a brief overview of the literature, original metabolomics data in a series of 92 primary breast cancer patients undergoing surgery at the Istituto Nazionale dei Tumori of Milano are reported highlighting a series of metabolic differences across various molecular subtypes. In particular, the difficult-to-treat luminal B subgroup represents a tumor type which preferentially relies on fatty acids for energy, whereas HER2 and basal-like ones show prevalently alterations in glucose/glutamine metabolism.

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“…Показано, что в гиппокампе мышей обеих линий белок ZDHHC21 визуализировался в виде полосы массой 32 кДа, что отличает ее от основной полосы массой 27 кДа, определяемой как основной бэнд белка ZDHHC21, экспрессируемый во фронтальной коре и среднем мозге. Можно предположить, что в гиппокампе происходят пострансляционные модификации ZDHHC21, что может играть существенную роль в регуляции функции белка (Varki, 1993;Dutta et al, 2017). В базе данных http://www.uniprot.org есть информация о пострансляционных модификациях только для пальмитилтрансферазы ZDHHC5 (http://www.uniprot.…”

Section: Discussionunclassified