Human cysteine proteinase inhibitors. Isolation, physiological importance, inhibitory mechanism, gene structure and relation to hereditary cerebral hemorrhage
Författare
Summary, in English
The isolation and characterization of six human cysteine proteinase inhibitors is reported. Their distribution in human biological fluids is also described and discussed with respect to physiological function. Studies on kininogen and cystatin C with respect to structure-function relationships and, as a result of the cystatin C studies, a general model for the mechanism of cysteine proteinase inhibition by cystatins are presented. The model was used for the construction of synthetic inhibitors which showed good inhibitory properties against papain and the streptococcal cysteine proteinase. Structures of cDNA and gene for normal human cystatin C are accounted for, as well as studies on the cystatin C gene in patients suffering from hereditary cystatin C amyloid angiopathy (HCCAA). As a result of this an RFLP that showed total co-segregation with the disease was found. It was concluded that the disease is caused by a point mutation in the cystatin C structural gene and that the RFLP will be a most useful tool for diagnosis of HCCAA. The production of recombinant cystatin C in E. coli is also reported and its possible use for treatment of HCCAA is discussed.
Avdelning/ar
Publiceringsår
1988
Språk
Engelska
Sidor
21-31
Publikation/Tidskrift/Serie
Scandinavian journal of clinical and laboratory investigation. Supplementum
Volym
48
Dokumenttyp
Artikel i tidskrift
Förlag
Taylor & Francis
Ämne
- Medicinal Chemistry
- Pharmacology and Toxicology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0085-591X