Fibrinogen Petoskey, a dysfibrinogenemia characterized by replacement of Arg-A alpha 16 by a histidyl residue. Evidence for thrombin-catalyzed hydrolysis at a histidyl residue

In this work, it is shown that the inherited dysfibrinogenemia, fibrinogen Petoskey, is due to an Arg arrow right His replacement at residue 16 in the A alpha chain of fibrinogen. This mutation involves the aminoacyl residue that provides the carbonyl portion of the peptide bond cleaved in the throm...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1981-12, Vol.256 (23), p.12013-12017
Main Authors: Higgins, D L, Shafer, J A
Format: Article
Language:English
Subjects:
Afibrinogenemia - blood
Afibrinogenemia - genetics
Amino Acids - analysis
Arginine
Carboxypeptidases
Fibrinogen - genetics
Fibrinogens, Abnormal
Histidine
Humans
Peptide Fragments - analysis
Thrombin - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In this work, it is shown that the inherited dysfibrinogenemia, fibrinogen Petoskey, is due to an Arg arrow right His replacement at residue 16 in the A alpha chain of fibrinogen. This mutation involves the aminoacyl residue that provides the carbonyl portion of the peptide bond cleaved in the thrombin-catalyzed release of fibrinopeptide A from fibrinogen in the conversion of fibrinogen to fibrin. Thrombin treatment of fibrinogen from patients with fibrinogen Petoskey, followed by high performance liquid chromatography, indicated that equal amounts of normal and an abnormal fibrinopeptide A were liberated from the patients' fibrinogen. This result indicates that the patients studied are heterozygotes with respect to their fibrinogen, which is consistent with the autosomal dominant mode of inheritance observed for their phenotypic prolonged thrombin clotting time. Amino acid analysis and carboxypeptidase Y digestion of the fibrinopeptides established the Arg arrow right His interconversion for fibrinogen Petoskey. The observation that thrombin catalyzes the hydrolysis of a histidyl peptide bond in the abnormal fibrinogen is the first report of a thrombin-catalyzed cleavage of a peptide bond other than at an arginyl or lysyl residue, and suggests that the arginyl residue in fibrinogen can bind to the active site of thrombin with its side chain extended in a conformation similar to that of a histidyl side chain.
ISSN:0021-9258
DOI:10.1016/S0021-9258(18)43225-5