Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency

Fuming Zhang; Andrew D Bries; Sybil C Lang; Qun Wang; David W Murhammer; John M Weiler; Robert J Linhardt

doi:10.1016/j.bbadis.2004.08.006

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Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency

Journal article

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Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency

Fuming Zhang, Andrew D Bries, Sybil C Lang, Qun Wang, David W Murhammer, John M Weiler and Robert J Linhardt

Biochimica et biophysica acta. Molecular basis of disease, Vol.1739(1), pp.43-49

2004

DOI: 10.1016/j.bbadis.2004.08.006

PMCID: PMC4137563

PMID: 15607116

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Abstract

Glycosylation, an important post-translation modification, could alter biological activity or influence the clearance rates of glycoproteins. We report here the first example of a heterozygous protein deficiency leading to metabolic alteration of N-glycan structures in residual secreted protein. Analysis of C1 esterase inhibitor (C1INH) glycans from normal individuals and patients with hereditary deficiency of C1INH demonstrated identical O-glycan structures but the N-glycans of patients with a heterozygous genetic deficiency were small, highly charged and lacked sialidase releasable N-acetylneuraminic acid. Structural studies indicate that the charge character of these aberrant N-glycan structures may result from the presence of mannose-6-phosphate residues. These residues might facilitate secretion of C1INH through an alternate lysosomal pathway, possibly serving as a compensatory mechanism to enhance plasma levels of C1INH in these deficient patients.

O-glycan

Glycosylation

N-glycan

Hereditary angioedema

C1 esterase inhibitor deficiency

C1 esterase inhibitor

Details

Title: Subtitle: Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency
Creators: Fuming Zhang - Department of Chemical and Biochemical Engineering, Iowa City, IA 52242, USA
Andrew D Bries - Department of Internal Medicine, College of Medicine, Iowa City, IA 52242, USA
Sybil C Lang - Department of Chemical and Biochemical Engineering, Iowa City, IA 52242, USA
Qun Wang - Division of Medicinal Chemistry, College of Pharmacy, Iowa City, IA 52242, USA
David W Murhammer - Department of Chemical and Biochemical Engineering, Iowa City, IA 52242, USA
John M Weiler - Department of Internal Medicine, College of Medicine, Iowa City, IA 52242, USA
Robert J Linhardt - Department of Chemical and Biochemical Engineering, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Biochimica et biophysica acta. Molecular basis of disease, Vol.1739(1), pp.43-49
DOI: 10.1016/j.bbadis.2004.08.006
PMID: 15607116
PMCID: PMC4137563
NLM abbreviation: Biochim Biophys Acta Mol Basis Dis
ISSN: 0925-4439
eISSN: 1879-260X
Publisher: Elsevier B.V
Language: English
Date published: 2004
Academic Unit: Chemical and Biochemical Engineering; Internal Medicine
Record Identifier: 9984003404502771

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