Aspartic proteinases in disease: A structural perspective

Cooper, J.B. (2002) Aspartic proteinases in disease: A structural perspective Current Drug Targets, 3, (2), pp. 155-173.


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The aspartic proteinases are a family of enzymes involved in a number of important biological processes. In animals the enzyme renin has a hypertensive action through its role in the renin-angiotensin system. The retroviral aspartic proteinases, such as the HIV proteinase, are essential for maturation of the virus particle and inhibitors have a proven therapeutic record in the treatment of AIDS. The lysosomal aspartic proteinase cathepsin D has been implicated in tumorigenesis and the stomach enzyme pepsin, which plays a major physiological role in hydrolysis of acid-denatured proteins, is responsible for much of the tissue damage in peptic ulcer disease. Since aspartic proteinases also play major roles in amyloid disease, malaria and common fungal infections such as candidiasis, inhibitors to these enzymes are much sought after as potential therapeutic agents. In all aspartic proteinases, the catalytic aspartate residues are involved in an intricate arrangement of hydrogen bonds involving a solvent molecule which is presumed to be water. The catalytic mechanism is thought to involve nucleophilic attack of the active site water molecule on the scissile bond carbonyl generating a tetrahedral gem-diol intermediate. The design of inhibitors generally involves the use of short oligopeptides containing a transition state analogue which mimic this tetrahedral intermediate. The application of structure-based drug design to members of the aspartic proteinase family is the main subject of this review.

Item Type: Article
ISSNs: 1389-4501 (print)
Related URLs:
Keywords: aspartic proteinasases, aids, amyloid disease, candidiasis, candida albicans, peptic ulcer disease, malaria, aspartic proteinase inhibitors, norstatine
Subjects: R Medicine > R Medicine (General)
Q Science > QH Natural history > QH301 Biology
ePrint ID: 56272
Date :
Date Event
1 April 2002Published
Date Deposited: 08 Aug 2008
Last Modified: 16 Apr 2017 17:41
Further Information:Google Scholar

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