Physiological variant of antithrombin‐III lacks carbohydrate sidechain at Asn 135

@article{Brennan1987PhysiologicalVO,
  title={Physiological variant of antithrombin‐III lacks carbohydrate sidechain at Asn 135},
  author={Stephen O. Brennan and Peter M. George and Robert E. Jordan},
  journal={FEBS Letters},
  year={1987},
  volume={219}
}
Both normal antithrombin‐III (AT‐IIIα) and the high heparin affinity form (AT‐IIIβ) were isolated from pooled human plasma. AT‐IIIβ had a lower negative charge and lower molecular mass than AT‐IIIα. Sialidase and endo‐F digestion indicated that the inherent difference resided in the oligosaccharide component of the molecule. CNBr fragmentation showed there was an oligosaccharide sidechain missing between residues 104 and 251, subdigestion with trypsin indicated that Asn 135 was not glycosylated… Expand
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References

SHOWING 1-10 OF 20 REFERENCES
Isolation and characterization of an antithrombin III variant with reduced carbohydrate content and enhanced heparin binding.
Two distinct forms of antithrombin III were isolated by chromatography of normal human plasma on heparin-Sepharose. The predominant antithrombin species present (AT-III alpha), which eluted from theExpand
Structural studies on the carbohydrate portion of human antithrombin III.
TLDR
The following structures is proposed for the carbohydrate chains in human antithrombin III: NeuNAc, N-acetylneuraminic acid; Galp, galactopyranose; GlcNAcp, 2-acetamido-2-deoxyglucopyrAnose; Manp, mannopyr anose are the abbreviations used in the structure. Expand
Antithrombin III Toyama: replacement of arginine-47 by cysteine in hereditary abnormal antithrombin III that lacks heparin-binding ability.
TLDR
Results suggest that arginine-47 is an essential amino acid residue for the binding with heparin in antithrombin III Toyama and that one base mutation, C leads to T, in the 5' terminal position of the arginin-47 genetic codon is probably responsible for this substitution. Expand
Purification of antithrombin III by affinity chromatography
Abstract Human antithrombin III has been purified from plasma by affinity chromatography on heparin-Sepharose gel. After further fractionation on DEAE-Sephadex and Sephadex G 200 a homogeneousExpand
alpha 1-Antitrypsin Christchurch, 363 Glu----Lys: mutation at the P'5 position does not affect inhibitory activity.
TLDR
In conclusion, antitrypsin Christchurch was isolated from the plasma of a Cambodian woman who was heterozygous for this variant and for the normal M protein, and both inhibitors were inactivated by catalytic amounts of papain. Expand
A simple two-step procedure for the isolation of antithrombin III from biological fluids.
TLDR
The results obtained illustrate not only is dextran sulphate capable of removing proteases most likely to complex with AT during heparin affinity chromatography but it can effectively remove preformed contaminating AT/protease complexes as well. Expand
Amino acid sequence analysis of the asparagine-288 region of the carbohydrate variants of human plasminogen.
TLDR
The basis for the lack of the complex-type oligosaccharide in human plasminogen variant 2 does not reside in substitution of essential amino acid residues in the region of the Asn288-linked glycosylation site. Expand
Development of Large Scale Fractionation Methods
Abstract. A large scale method for preparation of antithrombin III (AT III) concentrate from plasma or from Cohn fraction IV‐1 (Fr. IV‐1) has been described. It consists of the following steps: (a)Expand
The molecular abnormality of albumin Parklands: 365 Asp----His.
  • S. Brennan
  • Biology, Medicine
  • Biochimica et biophysica acta
  • 1985
TLDR
An electrophoretically slow albumin variant was isolated from the plasma of a patient with bisalbuminemia and confers on albumin Parklands a greater resistance to partial acid hydrolysis, a feature which, when employed together with SDS-gel electrophoresis, can be used as a diagnostic test for the presence of this variant. Expand
Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function.
TLDR
Two closely related crystal structures of alpha 1-proteinase inhibitor modified at the reactive site peptide bond Met358--Ser359 have been analysed, indicating a major structural rearrangement upon modification of the intact inhibitor. Expand
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