BIOTECH100
A Resource Guide to Investing in Biotechnology
Directory - Encyclopedia - Stock Index - Pipeline Drugs 

Biotechnology Encyclopedia

Protease

Peptidases (proteases [pronounced pro-tea-aces] and proteolytic enzymes are also commonly used) are enzymes which break peptide bonds of proteins. The process is called proteolytic cleavage. They use a molecule of water for this and are thus classified as hydrolases.

Classification

There are currently six classes of peptidases:

The Threonine and Glutamic peptidases was not described until 1995 and 2004, respectively. The mechanism used to cleave a peptide bond involve making an amino acid residue (serine, cystein and threonine peptidases) or a water molecule (aspartic, metallo and glutamic peptidases) nucleophilic so that it can attack the peptide carbonyl group. One way to make a nucleophile is by a catalytic triad, where a histidine residue is used to activate serine, cysteine or threonine as a nucleophile.

Occurrence

Peptidases occur naturally in all organisms and constitue 1-5% of the gene content. These enzymes are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated cascades (e.g. the blood clotting cascade, the complement system and the invertbrate prophenoloxidase activating cascade). Peptidases can break either specific peptide bonds (limited proteolysis), depending on the amino acid sequence of a protein, or break down a complete peptide to amino acids (unlimited proteolysis). The activity can be a destructive change abolishing a proteins function or digesting it to its principal components, it can be an activation of a function or it can be a signal in a signalling pathway.

Inhibitors

The function of peptidases is inhibited by protease inhibitor enzymes. Examples of protease inhibitors are the class of serpins (serine protease or peptidase inhibitors), incorporating alpha 1-antitrypsin. Other serpins are complement 1-inhibitor, antithrombin, alpha 1-antichymotrypsin, plasminogen activator inhibitor 1 (coagulation, fibrinolysis) and the recently discovered neuroserpin.

The natural protease inhibitors are not to be confused with the protease inhibitors used in antiretroviral therapy. Some viruses, with HIV among them, depend on proteases in their reproductive cycle. Thus, protease inhibitors are developed as antiviral means.

Degradation

As peptidases are themselves peptides, one natually wonders if they degrade themselves. In fact, many peptidases are known to cleave themselves or each other. This may be an important method of regulation of peptidase activity.

Peptidase research

The field of peptidase research is enormous and Barrett and Rawlings estimated that approximately 8000 papers related to this field were published each year.

References

  • Barrett AJ, Rawlings ND, Woessner JF. The Handbook of Proteolytic Enzymes, 2nd ed. Academic Press, 2003. ISBN 0120796104.
  • Hedstrom L. Serine Protease Mechanism and Specificity. Chem Rev 2002;102:4501-4523.
  • Southan C. A genomic perspective on human proteases as drug targets. Drug Discov Today 2001;6:681-688.
  • Hooper NM. Proteases in Biology and Medicine. London: Portland Press, 2002. ISBN 1855781476.
  • Puente XS, Sanchez LM, Overall CM, Lopez-Otin C. Human and Mouse Proteases: a Comparative Genomic Approach. Nat Rev Genet 2003;4:544-558.
  • Ross J, Jiang H, Kanost MR, Wang Y. Serine proteases and their homologs in the Drosophila melanogaster genome: an initial analysis of sequence conservation and phylogenetic relationships. Gene 2003;304:117-31.
  • Puente XS, Lopez-Otin C. A Genomic Analysis of Rat Proteases and Protease Inhibitors. Genome Biol 2004;14:609-622.

External links


 

 
Biotech100 Index
What are the Requirements to be listed in the Biotech100 Index?
 Biotech100 list of companies
Pipeline drugs for the Biotech100


Clinical Trials
What is a Clinical Trial?
Phase I ,-- Phase II, -- PhaseIII
What is Randomized Control?
 What is a Double Blind Experiment?
What is the role of the FDA?


Investing in Stocks
Small Cap Stocks
Stocks and Bonds
Biotech100 Index


Sponsored Links


Careers and Employment
Biotechnology and Pharmaceutical
What are the Fastest Growing Careers?

Key Biotech Terms


Google
 
Web www.biotech100.com
SEARCH THE BIOTECH100 WEBSITE
  
     

 
All text is available under the terms of the GNU Free Documentation License (see Copyrights for details). Disclaimers. Wikipedia is powered by MediaWiki, an open source wiki engine..
 


Copyright 2005 BIOTECH100.COM. All rights reserved.

email: info@biotech100.com