Protease A

Fig. 8. Protease washing performance in a U.S. liquid detergent. Grass soiling in a 10 min wash at 30°C with one enzyme dosage, (a) pH profile of commercial proteases A and B. (b) Effect of increasing ionic strength, adjusted with Na2S04, of commercial protease B at (—°—) pH 8 and (- pH 11.

James, M.N.G., et al. Structures of product and inhibitor complexes of Streptomyces griseus protease A at 1.8 A resolution. A model for serine protease catalysis. 

FIGURE 16.25 Structures of (a) HIV-1 protease, a dimer, and (b) pepsin (a monomer). Pepsin s N-terminal half is shown in red C-ter-minal half is shown in blue. 

The protease a-chymotrypsin has been used for transesterification reactions by two groups (Entries 7 and 8) [35, 36]. N-Acetyl-l-phenylalanine ethyl ester and N-acetyl-l-tyrosine ethyl ester were transformed into the corresponding propyl esters (Scheme 8.3-2). 

Puente XS, Sanchez LM, Overall CM et al (2003) Human and mouse proteases a comparative genomic approach. Nat Rev Genet 4 544—558... 

Rhinoviruses, which represent the single major cause of common cold, belong to the family of picornavimses that harbors many medically relevant pathogens. Inhibitors of the 3C protease, a cysteine protease, have shown good antiviral potential. Several classes of compounds were designed based on the known substrate specificity of the enzyme. Mechanism-based, irreversible Michael-acceptors were shown to be both potent inhibitors of the purified enzyme and to have antiviral activity in infected cells. 

Wlodaver A, Vondrasek J. Inhibitors of HIV-1 protease—a major success of structure-assisted drug design. Anna Rev Biophys Biomol Struct 1998 27 249-84. 

Bromomethyl-3,4-dibromo-3,4-dihydrocoumarin 1 (Fig. 11.4) and its chloro-methylated analogue 2b rapidly and progressively inactivate a-chymotrypsin and also the activities of a series of trypsin-like proteases. A benzyl substituent characteristic of good substrates of a-chymotrypsin was introduced at the 3-position to make inhibition more selective. This substituted dihydrocoumarin 3 irreversibly inhibited a-chymotrypsin and other proteases. These functionalized six-membered aromatic lactones, and their five- and seven-membered counterparts, 3//-benzofuran-2-ones 2a26 and 4,5-dihydro-3//-benzo[b]oxepin-2-ones 2c,27 were the first efficient suicide inhibitors of serine proteases. Their postulated mechanism of action is shown in Scheme 11.2. 

J. R. Huff, HIV Protease A novel chemotherapeutic target for AIDS, J. Med. Chem. 

Figure 17.5. The precursor molecule APP and the three different proteases a, (i, y secretase that are involved in the processing of APPto fS-amyloid peptide. The aberrant processing of the amyloid precursor protein (APP) leads to accumulation of beta-amyloid fragments, first as protofibrils and then as fibers that aggregate in the senile plaque structures. (See color insert.)...

Otto, B. R., Sijbrandi, R., Luirink, J., Oudega, B., Heddle, J. G., Mizutani, K., Park, S. Y., and Tame, J. R. (2005). Crystal structure of hemoglobin protease, a heme binding autotransporter protein from pathogenic Escherichia coli. f. Biol. Chem. 280, 17339-17345. 

Carbonate anhydrase (carbonic anhydrase, EC 4.2.1.1) catalyzes the reversible interconversion of C02 and HCO3 (see Sect. 3.7.3). The enzyme is found in erythrocytes, and in kidney and gastric juices where it contributes to the control of the acid-base balance. The esterase activity of carbonic anhydrase is probably due to the similarity between its active site and that of the zinc proteases. A possible physiological role of the esterase activity of this enzyme remains to be established. 

Serine proteases, see Trypsin, Chymotrypsin, Elastase, Strepto-myces griseus proteases A and B, or Subtilisin Southern bean mosaic virus protein (Abad-Zapatero et al., 1980) Jellyroll Greek key (3 barrel (Fig. 81)... 

Streptomyces griseus protease A (Brayer et al., 1978), see Trypsin Streptomyces griseus protease B (Delbaere et al., 1975), see Trypsin Subtilisin (Wright et al., 1969)... 

Dimmeler, S., Haendeler, J., GaUe, J., and Zeiher, A.M., 1997, Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-hke proteases. A mechanistic clue to the response to injury hypothesis, Circulation 95 1760-1763. 

General protease, a-amylase, and exoglucanase activities were estimated using hide powder-, amylose-, and celliilose-azure substrates, respectively, as described earlier (49). Here, standard curves were developed for the hydrolysis of each azure-linked substrate by standard enzymes of known activity. By this method, one cellulose-azure hydrolysis unit corresponds to one filter paper unit, one unit of hide powder-azure activity corresponds to the hydrolysis of 1.0 nmole of iV-benzoyl-L-tyrosine ethyl ester (BTEE) per min, and one amylose-azure unit of activity corresponds to the hydrolysis of 1.0 nmole of maltose from starch per 30 min. 

M.L. West, D. Fairlie, Targeting HIV-1 protease A test of drug-design methodologies. Trends Pharmacol. Sci. 16 (1995) 67-74. 

The pretreatment of wastewater with hydrolases or acids is one of the best ways to overcome this obstacle, because in this way the big polymer molecules can be decomposed to smaller units, which can be measured by the biosensor. The positive effect of an enzymatic pretreatment of wastewater prior to sensorBOD measurement was demonstrated [53, 66]. In these investigations, different types of wastewaters, which contained milk powder, starch, or cellulose, were treated by proteases, a-amylases, and cellulases or a mix of these enzymes, respectively. This pretreatment resulted in a good correlation between sensorBOD and the conventional five-day BOD, while the sensorBOD values for untreated wastewater were significantly lower (see Table 6). As an example, the sensorBOD of a wastewater from a paper factory increased approximately to the fourfold value when treated by a mixture of cellulase and -glucosidase. 

Kasche, V. (1989) Proteases in peptide synthesis. In Proteases a Practical Approach, edited by U.Bond and R.Beynon, pp. 125-143. Oxford IRL Press. 

Naturally occurring Upases are (R)-selective for alcohols according to Kazlauskas rule [58, 59]. Thus, DKR of alcohols employing lipases can only be used to transform the racemic alcohol into the (R)-acetate. Serine proteases, a sub-class of hydrolases, are known to catalyze transesterifications similar to those catalyzed by lipases, but, interestingly, often with reversed enantioselectivity. Proteases are less thermostable enzymes, and for this reason only metal complexes that racemize secondary alcohols at ambient temperature can be employed for efficient (S)-selective DKR of sec-alcohols. Ruthenium complexes 2 and 3 have been combined with subtilisin Carlsberg, affording a method for the synthesis of... 

Reddy RM, Varney MD, Kalish V, Viswanadhan VN, Appelt K. Calculation of relative differences in the binding free energies of HIV-1 protease a thermodynamic cycle perturbation approach. J. Med. Chem. 1994 37 1145-1152. 

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