Insight into the structure, function, and biosynthesis of factor VIII through recombinant DNA technology

1991 ◽  
Vol 63 (3) ◽  
pp. 155-165 ◽  
Author(s):  
Randal J. Kaufman
2005 ◽  
Vol 33 (4) ◽  
pp. 811-814 ◽  
Author(s):  
S. Frank ◽  
A.A. Brindley ◽  
E. Deery ◽  
P. Heathcote ◽  
A.D. Lawrence ◽  
...  

The anaerobic biosynthesis of vitamin B12 is slowly being unravelled. Recent work has shown that the first committed step along the anaerobic route involves the sirohydrochlorin (chelation of cobalt into factor II). The following enzyme in the pathway, CbiL, methylates cobalt-factor II to give cobalt-factor III. Recent progress on the molecular characterization of this enzyme has given a greater insight into its mode of action and specificity. Structural studies are being used to provide insights into how aspects of this highly complex biosynthetic pathway may have evolved. Between cobalt-factor III and cobyrinic acid, only one further intermediate has been identified. A combination of molecular genetics, recombinant DNA technology and bioorganic chemistry has led to some recent advances in assigning functions to the enzymes of the anaerobic pathway.


1999 ◽  
Vol 82 (08) ◽  
pp. 505-508 ◽  
Author(s):  
Pete Lollar

IntroductionFactor VIII contains three epitopes that are the usual targets of clinically significant antibody inhibitors. Two of these epitopes are located in the A2 and C2 domains of factor VIII. The third epitope appears to be in the A3 domain. Ongoing studies continue to provide higher resolution maps of these epitopes and to understand the mechanism by which inhibitors produce a bleeding diathesis. The manipulation of inhibitor epitopes using recombinant DNA technology may lead to improved forms of factor VIII that have lower antigenicity and/or lower immunogenicity.


1992 ◽  
Vol 38 (Special) ◽  
pp. 263-266
Author(s):  
O. IFUKU ◽  
S. HAZE ◽  
J. KISHIMOTO ◽  
M. YANAGI

PEDIATRICS ◽  
1984 ◽  
Vol 74 (3) ◽  
pp. 408-411
Author(s):  
Stephen D. Cederbaum

Seldom has a scientific or biomedical break-through evoked the awe, controversy, or sheer incredulity that has accompanied the developments in the field of recombinant DNA technology or more popularly, gene cloning and genetic engineering. Now little more than one generation after Avery, et al1 demonstrated that genes were encoded in DNA and Watson and Crick2 interpreted the structure of these molecules, genes are being cut, manipulated, and recombined to produce unprecedented new insights into genetics and molecular biology and the prospect of gene therapy. These developments have not occurred without anxiety to both scientists and laymen. At the moment, neither the most apocalyptic fears nor the most optimistic dreams appear to be imminent, although I believe that the dreams are closer to fulfillment than the fears. Recombinant DNA technology is already having great impact in hematology, oncology, endocrinology, immunology, and infectious disease and will soon play an important role in other medical subspecialities as well. In none, however, will it have quite the same impact as in genetics because DNA is the material that genetics "is all about." The cloning and study of phenylalanine hydroxylase is one of the first instances in which this technology has important implications in the diseases traditionally classified as inborn errors of metabolism. In order to understand and appreciate the presentation by Woo on phenylalanine hydroxylase as well as the many future papers that will play so vital a role in all of our professional lives, it is necessary to acquire the basic vocabulary of the field.


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