Interaction of α-Chymotrypsin with Several α-Methyl-α-Acylamino Acid Methyl Esters<sup>*</sup>

Almond, Harold R.; Manning, David T.; Niemann, Carl

doi:10.1021/bi00908a008

Cited by 40 publications

(11 citation statements)

References 21 publications

(12 reference statements)

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“…It may be important, however, that the acylamino group is kept well away from the catalytic functionalities and the susceptible carbonyl group of the substrate. This was indicated some time ago by Almond, Manning & Niemann (1962), who found that a-Cmethyl-N-acyl-a-amino acid esters bind normally to a-chymotrypsin, but have catalytic constants at least 105-fold lower than those of the corresponding substrates where the a-methyl group is replaced by hydrogen. Further information on this question must wait for more detailed crystallographic studies of substrate and inhibitor binding to the enzyme than are presently available (Matthews, Sigler, Henderson & Blow, 1967).…”

Section: Discussionmentioning

confidence: 95%

The stereospecificity of α-chymotrypsin

Ingles

Knowles

1968

Biochemical Journal

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1. The rates of deacylation of acyl-alpha-chymotrypsins in which the hydrogen-bonding capacity of the acylamino group of the substrate has been systematically removed were measured. 2. The ratio of deacylation rates of l- and d-acyl-enzymes is found to depend largely on the existence in the substrate of an amido -NH- group. 3. The data presented agree with the postulate that the stereospecificity of alpha-chymotrypsin is exercised in catalytic rather than binding steps, and that the active site of the enzyme presents three loci to the substrate: the site containing the catalytic functionalities (including serine-195), the hydrophobic area for amino acid side-chain binding, and a hydrogen-bond acceptor site for acylamino group binding. 4. It is noted that, though the hydrogen-bonding site is crucial for the stereospecificity, the free energy of binding of substrates and inhibitors is dominated by the hydrophobic interaction. 5. It is tentatively proposed that alpha-chymotrypsin selects a high-energy conformation of the substrate when the latter binds at the enzyme's active site.

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Section: Discussionmentioning

confidence: 95%

The stereospecificity of α-chymotrypsin

Ingles

Knowles

1968

Biochemical Journal

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“…The lack of reactivity of methyl a-acetamidoisobutyrate establishes the fact that the decrease in values of ko associated with the placing of an alkyl group in the pH position, previously observed with a-A/'-acyl-amethyl aromatic -amino acid esters (Almond et al, 1962), also obtains in the case of a-IV-acyl-a-methyl aliphatic -amino acid esters. There is little doubt that the inertness of methyl a-acetamidoisobutyrate as a substrate arises from a very high Ko value and a very low ko value.…”

Section: Discussionmentioning

confidence: 60%

The α-Chymotrypsin-Catalyzed Hydrolysis of a Series of Analogs of Acetylglycine Methyl Ester^*

Wolf¹,

Niemann²

1963

Biochemistry

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“…Steric effects arising from the structure of the substrate molecule have been encountered earlier Roger l. peterson, konrad w. hubele, and carl niemann Biochemistry (Almond et al, 1962;Wolf and Niemann, 1963b; Waite and Niemann, 1962; Jones and Niemann, 1962;Abrash, 1961). They have arisen from replacement of the -hydrogen atom by a bulkier group or by ßbranching of the side chain of both aliphatic and aromatic a-N-acylated--amino acid derivatives.…”

Section: Discussionmentioning

confidence: 85%

The α-Chymotrypsin-catalyzed Hydrolysis of α-N and O-Alkyl Derivatives of α-N-Acetyl-L-tyrosine Methyl Ester^*

Peterson¹,

Hubele²,

Niemann³

1963

Biochemistry

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An investigation of the kinetics of the -chymotrypsin-catalyzed hydrolysis of --acetyl--jV-methyl-L-tyrosine methyl ester and of --acetyl-O-methyl, -ethyl, and -isopropyl-Ltyrosine methyl ester, in aqueous solutions at 25.0°, pH 7.90, and 0.10 m in sodium chloride, has shown that the lesser reactivity of these substrates, relative to -lV-acetyl-L-tyrosine methyl ester, is not due to an inability of the modified molecules to combine with the active site of the enzyme. The diminished reactivity arises from a less favorable orientation of the modified molecules when present at the active site. «-.ZV-Acylated aromatic -amino acid esters are among the more reactive substrates of a-chymotrypsin and are frequently employed in studies on the mechanism of action of this enzyme. However, there are many features of the structural specificity of a-chymo-

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Interaction of α-Chymotrypsin with Several α-Methyl-α-Acylamino Acid Methyl Esters^*

Cited by 40 publications

References 21 publications

The stereospecificity of α-chymotrypsin

The stereospecificity of α-chymotrypsin

The α-Chymotrypsin-Catalyzed Hydrolysis of a Series of Analogs of Acetylglycine Methyl Ester^*

The α-Chymotrypsin-catalyzed Hydrolysis of α-N and O-Alkyl Derivatives of α-N-Acetyl-L-tyrosine Methyl Ester^*

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Interaction of α-Chymotrypsin with Several α-Methyl-α-Acylamino Acid Methyl Esters*

Cited by 40 publications

References 21 publications

The stereospecificity of α-chymotrypsin

The stereospecificity of α-chymotrypsin

The α-Chymotrypsin-Catalyzed Hydrolysis of a Series of Analogs of Acetylglycine Methyl Ester*

The α-Chymotrypsin-catalyzed Hydrolysis of α-N and O-Alkyl Derivatives of α-N-Acetyl-L-tyrosine Methyl Ester*

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Product

Resources

About

Interaction of α-Chymotrypsin with Several α-Methyl-α-Acylamino Acid Methyl Esters^*

The α-Chymotrypsin-Catalyzed Hydrolysis of a Series of Analogs of Acetylglycine Methyl Ester^*

The α-Chymotrypsin-catalyzed Hydrolysis of α-N and O-Alkyl Derivatives of α-N-Acetyl-L-tyrosine Methyl Ester^*