Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity

Structural studies on a hereditary abnormal prothrombin, prothrombin Salakta, have been performed to identify the difference responsible for its reduced fibrinogen clotting activity and its reduced esterase activity. Amino acid composition and sequence analyses of a peptide isolated from a lysylendo...

Full description

Saved in:
Bibliographic Details
Published in:Biochemistry (Easton) 1992-08, Vol.31 (33), p.7457-7462
Main Authors: Miyata, Toshiyuki, Aruga, Rie, Umeyama, Hideaki, Bezeaud, Annie, Guillin, Marie Claude, Iwanaga, Sadaaki
Format: Article
Language:English
Subjects:
activity
Alanine
Amino Acid Sequence
Analytical, structural and metabolic biochemistry
Base Sequence
Biological and medical sciences
carboxylesterase
clotting
Codon - genetics
Enzymes and enzyme inhibitors
Esterases - blood
Fibrinogen - metabolism
Fundamental and applied biological sciences. Psychology
Glutamates
Glutamic Acid
Humans
Hydrolases
Models, Molecular
Molecular Sequence Data
Mutation
Peptide Fragments
Protein Conformation
prothrombin
Prothrombin - chemistry
Prothrombin - genetics
Prothrombin - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Structural studies on a hereditary abnormal prothrombin, prothrombin Salakta, have been performed to identify the difference responsible for its reduced fibrinogen clotting activity and its reduced esterase activity. Amino acid composition and sequence analyses of a peptide isolated from a lysylendopeptidase digest of the abnormal thrombin indicated that Glu-466 had been replaced by Ala. This amino acid substitution can result from a single nucleotide change in the codon for Glu-466 (GAG---GCG). The model building and the molecular dynamics simulation of thrombin Salakta suggest that the Glu-466---Ala substitution would change the proper conformation around the substrate binding site containing Trp-468, which is a unique surface loop on the thrombin molecule. This is the experimental and theoretical evidence supporting the role of the surface loop containing Trp-468 for the proper conformation of the substrate binding site.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00148a005