Abstract |
In an abnormal fibrinogen with severely impaired polymerization of fibrin monomers, we identified a methionine-to- threonine substitution at position 310 of the gamma chain. Furthermore, asparagine at position 308 was found to be N-glycosylated due to a newly formed consensus sequence, asparagine(308)-glycine(309)-threonine(310). The two structural defects in the mutant gamma chain may well perturb the conformation required for fibrin monomer polymerization that is specifically assigned to the D domain of fibrinogen. This alteration also seems to affect the intermolecular gamma chain cross-linking of fibrin and fibrinogen, although the amine acceptor gamma glutamine-398 was found to function normally. These functional abnormalities may well be related to posttraumatic hemorrhage as observed in a 33-yr-old man with moderate hemorrhagic diathesis related to injuries since his early adolescence. The structure of the extra carbohydrate moiety attached to asparagine-308 was found to be identical with those derived from the normal B beta and gamma chains as evidenced by HPLC.
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Authors | K Yamazumi, K Shimura, S Terukina, N Takahashi, M Matsuda |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 83
Issue 5
Pg. 1590-7
(May 1989)
ISSN: 0021-9738 [Print] United States |
PMID | 2496144
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fibrinogens, Abnormal
- Oligosaccharides
- Peptide Fragments
- fibrinogen Asahi
- Threonine
- Asparagine
- Methionine
- Thrombin
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Topics |
- Adult
- Amino Acid Sequence
- Asparagine
- Binding Sites
- Carbohydrate Conformation
- Carbohydrate Sequence
- Chromatography, High Pressure Liquid
- Fibrinogens, Abnormal
(isolation & purification, metabolism)
- Glycosylation
- Hemorrhagic Disorders
(blood, congenital, genetics)
- Humans
- Male
- Methionine
- Molecular Sequence Data
- Mutation
- Oligosaccharides
- Peptide Fragments
(isolation & purification, metabolism)
- Threonine
- Thrombin
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