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A molecular model for the triplicated A domains of human factor VIII based
on the crystal structure of human ceruloplasmin
S Pemberton, P Lindley, V Zaitsev, G Card, EG Tuddenham and G Kemball-Cook
Haemostasis Research Group, Medical Research Council Clinical Sciences
Centre, London, UK.
The hemophilia A mutation database lists more than 160 missense mutations:
each represents a molecular defect in the FVIII molecule, resulting in the
X-linked bleeding disorder hemophilia A with a clinical presentation
varying from mild to severe. Without a three- dimensional FVIII structure
it is in most cases impossible to explain biological dysfunction in terms
of the underlying molecular pathology. However, recently the crystal
structure of the homologous human plasma copper-binding protein
ceruloplasmin (hCp) has been solved, and the A domains of FVIII share
approximately 34% sequence identity with hCp. This advance has enabled the
building of a molecular model of the A domains of FVIII based on the
sequence identity between the two proteins. The model allows exploration of
predictions regarding the general features of the FVIII molecule, such as
the binding-sites for factor IXa and activated protein C; it has also
allowed the mapping of more than 30 selected mutations with known phenotype
from the database, and the prediction of hypothetical links to dysfunction
in all but a few cases. A computer-generated molecular model such as that
reported here cannot substitute for a crystal structure. However, until
such a structure for FVIII becomes available, the model represents a
significant advance in modeling FVIII; it should prove a useful tool for
exploiting the increasing amount of information in the hemophilia A
mutation database, and for selecting appropriate targets for investigation
of the structure-function relationships via mutagenesis and expression in
vitro.
Volume 89,
Issue 7,
pp. 2413-2421,
04/01/1997
Copyright © 1997 by The American Society of Hematology
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|
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