Proteases function

Denmeade SR, Lovgren J, Khan SR, Lilja H, Isaacs JT. Activation of latent protease function of pro-hK2, but not pro-PSA, involves autoprocessing. Prostate 2001 48 122-126. 

Unlike other proteases, the proteasome utilizes threonine protease activity. The N-terminal threonines act as active nucleophiles that attack the amide carbonyl moiety of target proteins, cleave the amide bond to form an acyl-enzyme intermediate, and subsequently hydrolyze to release the free proteasome threonine residue and the remaining peptide residue. Small molecules, including natural product-based proteasome inhibitors have significantly contributed to our understanding of the specifics of proteasome protease function (reviewed by Tsukamoto and Yokosawa ). 

Protease inhibitors, which are the most potent antiretroviral agents currently available, were the end result of coordinated chemical design and structure-based computational analysis of the protease enzyme. With identification of the protease crystalline structure and identification of active binding sites, scientists were able to create compounds that would fit the protease enzyme with strong affinity and cause an inhibition of protease function. The clinical impact of these man-made drugs is... 

A comprehensive treatment of tautomerism and ionisation in structural databases requires storage of the different forms in which a compound can exist, as well as values of pKa (some proteases function in the acidic interior of the lysosome) and tautomeric ratios. Automatic prediction of pKa and... 

Some proteases function as digestive enzymes. They usually occur extracellu-larly, in the gastro-intestinal tract, but some animals secrete proteases to the outside of their bodies. Intracellularly occurring proteases.have been studied relatively little they are called cathepsins. 

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