Chymotrypsin, hydrolysis catalyzed

Site of chymotrypsin catalyzed hydrolysis when R is an aromatic side chain... 

The a-chymotrypsin-catalyzed hydrolysis of the p-nitroanilide group in acrylamide copolymers with monomer I proceeds with a rate comparable to that of the monomer... 

FIGURE 1 Effects of small structural changes in the substrate on kinetic parameters for chymotrypsin-catalyzed amide hydrolysis. 

The above cyclic sulfates and 4-nitrocatechol cyclic sulfate are good substrates for a-chymotrypsin and carbonic anhydrase138-138. In the case of the chymotrypsin-catalyzed hydrolysis of (73) to the product acid, a rapid sul-fonylation of the active site of the enzyme to give (74) occurs, viz. 

Figure 7.3 The chymotrypsin-catalyzed hydrolysis and transacylation reactions of Ac-Phe-OCH3 in the presence of various concentrations of Ala-NH2. The values of fccat for the depletion of Ac-Phe-OCH3 and the production of Ac-Phe and Ac-Phe-Ala-NH2 are calculated from equation 7.3 by using k2 = 2200 s 1, 3 [H20] = 144 s-1, and kA = 6340 S M l. [From J. Fastrez and A. R. Fersht, Biochemistry 12, 2025 (1973).]...

Fersht, A. R., D. M. Blow, and J. Fastrez, Leaving group specificity in chymotrypsin-catalyzed hydrolysis of peptides A stereochemical interpretation. Biochem. 12 2035, 1973. 

Petkov and Stoineva (12) have more recently reported that the relative rate of the o-chymotrypsin-catalyzed hydrolysis of p-alkoxycarbonyl anilide derivatives 35 of N-acetyl-(.-phenylalanine is enhanced with an increase in the size of the R alkyl group of the leaving group. This rate enhancement specificity appears to be entropy controlled the bulky alkyl groups increase both enthalpy and entropy of activation. These kinetic and thermodynamic data were interpreted in the following way the bulky -alkoxycarbonyl... 

Kinetic studies of a-chymotrypsin catalyzed hydrolysis of p-nitrophenyl esters are carried out (Duprix et al., 1970) ... 

Perform the regression analyses for the descriptors to assess the contribution of substituent effect(s) on the rate of a-chymotrypsin-catalyzed hydrolysis of p-nit-rophenyl esters. Referring to the catalytic triad of chymotrypsin, rationalize your results for the plausible reaction mechanism. 

IM-OH cooperation. It is interesting that the appearance of a cooperation between imidazole and hydroxyl moieties in the synthetic polymer is found, as is observed in a-chymotrypsin-catalyzed hydrolysis. The cooperation is ascertained in the hydrolyses catalyzed by copolymers of 4 5)-vinylimidazole with vinyl alcohol, poly(IM-al) (VI), and with p-vinylphenol, poly(IM-ph) (VII) (77, 78). 

Zamai et al. from the same company have also published data on sequence-directed peptide inhibitors [80]. They used the model of big ET-1 which they proposed on the basis of computerized structure prediction, molecular mechanics minimization and molecular dynamics [81]. The effect of the sequence-directed inhibitors on the in vitro chymotrypsin-catalyzed hydrolysis of big ET-1 was investigated as a strategy for inhibiting formation of endothelin. 

This intermediate is formed during the a-chymotrypsin-catalyzed hydrolysis of esters, by the following reaction scheme ... 

This represents direct evidence for the existence of a presumably covalent acyl-enzyme intermediate in the a-chymotrypsin-catalyzed hydrolysis of a specific substrate (Fink, 1973b). 

A Schematic View of the Mechanism of Chymotrypsin-Catalyzed Amide Hydrolysis Occurring at the Enzyme Active Site... 

The known desymmetrization of prochiral 3-substituted glutarates via enzymatic hydrolysis [65] has been optimized by chemists at Ciba Speciality Chemicals for the synthesis on a large scale [66]. The a-chymotrypsin-catalyzed process is characterized by a high substrate concentration of 285 g L and an isolated yield of 94% product with an ee of 98.2% (route C). 

The rate of a-chymotrypsin-catalyzed hydrolysis as a function of overall GPANA concentration in CTAB reversed micelles and in aqueous solution are shown in Figure 5. It is apparent that the reaction rate in the reversed micellar solution is on the order of 50 times more rapid than in the aqueous system. Furthermore, in the reversed micellar system there is no indication of enzyme saturation as the reaction is first order in substrate concentration. As enzyme saturation kinetics are not observed, it is impossible to differentiate between the parameters kcat and Kg. Instead a second order bimolecular rate constant for both the micelle interior ( micelle) and for what is experimentally observed ( observed) is defined. 

Chymotrypsin catalyzes the hydrolysis of peptide bonds adjacent to aromatic amino acids. The probable mechanism for this reaction is illustrated in Figure 6.19. Step (a) of the figure shows the initial enzyme-substrate complex. Asp 102, His 57, and Ser 195 are aligned. In addition, the aromatic ring of the substrate s phenylalanine residue is seated in a hydrophobic binding pocket, and... 

You will find a proposed mechanism for how chymotrypsin catalyzes the hydrolysis of certain peptide bonds in protein molecules at the textbook s Web site. 

Examples of enantioselective hydrolysis of cyclic diesters by a-chymotrypsin are comparatively rare (10-14) (Table 11.1-7). Interestingly, the cyclopentanoid and the cyclohexenoid monoesters 11 and 12 have the opposite absolute configuration to those obtained by the pig liver esterase-catalyzed hydrolysis of the corresponding diesters (Table 11.1-1). The keto ester 14, which is a valuable building block for the synthesis of prostacyclin analogs, has been obtained from the corresponding a,a -keto diester via a-chymotrypsin-catalyzed hydrolysis followed by a decarboxylation of the keto acid. 

Chymotrypsin catalyzes the hydrolysis of the peptide bond on the C-side of amino acids that contain aromatic six-membered rings (Phe, Tyr, Trp). 

The mechanism for bovine chymotrypsin-catalyzed hydrolysis of a peptide bond is shown in Figure 24.7. The other serine proteases follow the same mechanism. The reaction proceeds as follows ... 

The mechanism for chymotrypsin-catalyzed hydrolysis shows the importance of histidine as a catalytic group. Because the pA a of the imidazole ring of histidine (pTTa = 6.0) is close to neutrality, histidine can act both as a general-acid catalyst and as a general-base catalyst at physiological pH. 

Proposed mechanism for the chymotrypsin-catalyzed hydrolysis of a peptide bond. 

Cyclodextrins, however, show no enantiomeric specificity in the deacylation step. The rate of hydrolysis of acyl-a-cyclodextrin derived from the (-I-) enantiomer of (14a) is equal to that derived from the ( —) enantiomer. This can be associated with the fact that the nitroxide function is not included in the cyclodextrin cavity, as shown by electron spin resonance. In the a-chymotrypsin-catalyzed hydrolysis of (14b), however, the acyl enzyme derived from the (-I-) enantiomer hydrolyzes 21 times faster than the acyl enzyme derived from the (—) enantiomer. 

In a study of an a-chymotrypsin-catalyzed reaction, the maximum rate of hydrolysis, V, was found to vary with pH as follows ... 

It was found by Hartley and Kilby 11) that chymotrypsin catalyzes the hydrolysis of p-nitrophenyl acetate. From a study of the kinetics of the hydrolysis of p-nitrophenyl acetate 6) and 2,4-dinitro-phenyl acetate... 

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