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Chymotrypsin charge-relay system

Figure 7-7. Catalysis by chymotrypsin. The charge-relay system removes a proton from Ser 195, making it a stronger nucleophile. Activated Ser 195 attacks the peptide bond, forming a transient tetrahedral intermediate. Release of the amino terminal peptide is facilitated by donation of a proton to the newly formed amino group by His 57 of the charge-relay system, yielding an acyl-Ser 195 intermediate. His 57 and Asp 102 collaborate to activate a water molecule, which attacks the acyl-Ser 195, forming a second tetrahedral intermediate. The charge-relay system donates a proton to Ser 195, facilitating breakdown of tetrahedral intermediate to release the carboxyl terminal peptide . Figure 7-7. Catalysis by chymotrypsin. The charge-relay system removes a proton from Ser 195, making it a stronger nucleophile. Activated Ser 195 attacks the peptide bond, forming a transient tetrahedral intermediate. Release of the amino terminal peptide is facilitated by donation of a proton to the newly formed amino group by His 57 of the charge-relay system, yielding an acyl-Ser 195 intermediate. His 57 and Asp 102 collaborate to activate a water molecule, which attacks the acyl-Ser 195, forming a second tetrahedral intermediate. The charge-relay system donates a proton to Ser 195, facilitating breakdown of tetrahedral intermediate to release the carboxyl terminal peptide .
Crystallographic studies (Blow, 1976) of the structure of the enzyme, enzyme-substrate complexes and enzyme-product complexes have identified a common feature in catalysis by the serine protease enzymes such as a-chymotrypsin. This is the well-known charge-relay system (44), in which... [Pg.354]

The structural analysis has been carried out right up to the recognition of molecular Level (i, 2). a-Chymotrypsin is poly(amino acid) consisting of 245 amino adds, having relatively deep grooves. It catalyzes the hydrolysis of carboxylic acid derivatives such as protein, simple amides, esters, etc. The active site is composed of aspartic add, Asp (102). .. histidine, His (57). .. serine, Ser (195), and the distances between Asp. .. His and His... Ser are 2.8 A and 3.0 A, respectively. Electronic structures of these moieties depend on the pH of the reaction system. In the range of pH > 7 at which a-chymotrypsin is active, —COO" of Asp attracts N4 proton in imidazolyl of His, and Nj in the imidazolyl of His attracts the proton in OH of Ser. It is called charge-relay system . [Pg.57]

Essentially, a-chymotrypsin has these characteristics the selectivity in the substrate binding, the charge-relay system in the active center and a contribution of the bound substrate to the catalysis, as cooperativities. [Pg.58]

The charge relay system is found at the active site of a group of enzymes called serine proteases. They include chymotrypsin, trypsin, a-lytic protease, elastase, and subtilisin. It is interesting that the charge relay system was found in enzymes belonging to different branches of diemical evolution (chymotrypsin and subtilisin). This suggests that this system is a hydrolytic catalytic system of general importance which is derived solely from amino acid residues. [Pg.164]

A more complete but more speculative picture of the reactive site of the lipase (Figure 4) (12) shows the hydrophobic leucine next to the reactive serine. I suggest that the leucine is not buried inside the enzyme but exposed on the surface and held in place by steric restriction or hydro-phobic binding by another amino acid. The leucine could then contribute not only to the hydrophobicity of the reactive site but also to its sterically hindered nature. An aspartic acid residue in chymotrypsin assists in the activation of the nucleophilic serine hydroxyl through a charge relay system. Lipase may have a similar system, and aspartic acid is therefore included in the model (Figure 4). [Pg.137]

More than a third of all known proteolytic enzymes are serine proteases (2). The family name stems from the nucleophilic serine residue within the active site, which attacks the carbonyl moiety of the substrate peptide bond to form an acyl-enzyme intermediate. Nucleophilicity of the catalytic serine is commonly dependent on a catalytic triad of aspartic acid, histidine, and serine—commonly referred to as a charge relay system (3). First observed by Blow over 30 years ago in the structure of chymotrypsin (4), the same combination has been found in four other three-dimensional protein folds that catalyze hydrolysis of peptide bonds. Examples of these folds are observed in trypsin. [Pg.1706]

Subtilisin (see) from Bacillus subiilis is a S.p. it resembles chymotrypsin in the hydrogen bonding of the charge-relay system, but is otherwise structurally dissimilar it is thus an example of convergent evolution of a catalytic center in two different groups of proteins. [Pg.626]

Figure 1 shows a plot of ccr vs pH for histidine-57 of a-chymotrypsin and chymotrypsinogen. This residue is the catalytic site histidine and has been postulated to be involved in a charge-relay system [5] via hydrogen bonding with aspartic-102 and serine-195. The features of interest are ... [Pg.411]

In the three-dimensional structure of chymotrypsin, the serine residue (which is residue 195 from the N-terminus of the chain and is hence termed serine-195) is located in close proximity to the residues histidine-57 and aspartate-102. The negatively charged aspartate-102 tends to withdraw a proton from the imidazole ring of histidine-57 adjacent to it. The imidazole ring then attracts a proton from serine-195. The effect of this charge relay system is to lower the effective pK of serine-195 and thus make it more reactive... [Pg.86]

A simplified reaction mechanism for chymotrypsin is shown in Figure 6.11. The carbonyl carbon atom of the peptide bond to be hydrolysed is subject to attack by the polarized oxygen atom of serine-195. An acylenzyme intermewater molecule then enters and is polarized by the charge relay system. The hydroxyl residue attacks the carbonyl carbon of the acyl group attached to serine-195, with the hydrolysis of the acylenzyme intermediate and release of the product. [Pg.86]

However, on the basis of the crystallographic structure for a-chymotrypsin, a new form of general catalysis was proposed. It is called the charge-relay system and originates with the alignment of Asp-102, His-57, and Ser-195, linked by hydrogen bonds (Fig. 4.3). [Pg.209]

Fig. 4.3. The charge-relay system of a-chymotrypsin (position 3 of the imidazole group is often referred to as N l or 7t and position 1 as Ne2 or t). Fig. 4.3. The charge-relay system of a-chymotrypsin (position 3 of the imidazole group is often referred to as N l or 7t and position 1 as Ne2 or t).
The catalytic efficiency of a-chymotrypsin cannot be solely attributed to the presence of the charge-relay system. X-Ray work (81) has indicated the many parameters operative in the catalytic process. Nine specific enzyme substrate interactions have been identified in making the process more efficient. For example, stabilization of the tetrahedral intermediate, and thus lowering of the transition state energy barrier, is accomplished by hydrogen bond formation of the substrate carbonyl function with the amide hydrogen... [Pg.211]

Comparison (or alignment) of amino acid sequences, also called homology search, often provides first-hand information on such conserved structural features and enables one to classify enzymes into families and predict the possible function of a new enzyme (86). A family of enzymes usually folds into similar 3-D structures, at least at the active site region. A typical example is the serine protease family whose members—trypsin, chymotrypsin, elastase, and subtilisin—commonly contain three active-site residues, Asp/His/Ser, which are known as the catalytic triad or charge relay system. Another example is the conserved features of catalytic domains of the highly diverse protein kinase family. In this kinase family, the ATP-binding (or phosphate-anchoring) sites present a consensus sequence motif of Gly-X-Gly-X-X-Gly (67,87). [Pg.27]

In chymotrypsin and subtilisin, this charge-relay network system, as it is called, is made up of a specific aspartic acid residue, acting as B e, and a specific histidine residue (acting as the amphoteric B—A—H) ... [Pg.1266]


See other pages where Chymotrypsin charge-relay system is mentioned: [Pg.202]    [Pg.191]    [Pg.37]    [Pg.264]    [Pg.292]    [Pg.60]    [Pg.37]    [Pg.102]    [Pg.124]    [Pg.124]    [Pg.191]    [Pg.848]    [Pg.52]    [Pg.310]    [Pg.1460]    [Pg.202]    [Pg.521]    [Pg.224]    [Pg.163]    [Pg.220]    [Pg.374]    [Pg.556]    [Pg.521]    [Pg.109]    [Pg.87]    [Pg.218]    [Pg.305]    [Pg.239]    [Pg.507]    [Pg.129]   
See also in sourсe #XX -- [ Pg.475 ]




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