Inhibition of the esterase action of carboxypeptidase A

Kaiser, E. T.; Carson, Frederick W.

doi:10.1016/0006-291x(65)90773-4

Cited by 19 publications

(11 citation statements)

References 7 publications

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“…Maximum error in K is about 11 %. 6 Ki = 6.2 10-5 m against CGP (Elkins-Kaufman and Neurath, 1949); Ki = 1.52 X 10"4 m against hippuryl-L-mandelate (Kaiser and Carson, 1965).…”

Section: Resultsmentioning

confidence: 99%

Binding of the by-product analog benzylsuccinic acid by carboxypeptidase A

Byers¹,

Wolfenden²

1973

Biochemistry

216

108

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“…Maximum error in K is about 11 %. 6 Ki = 6.2 10-5 m against CGP (Elkins-Kaufman and Neurath, 1949); Ki = 1.52 X 10"4 m against hippuryl-L-mandelate (Kaiser and Carson, 1965).…”

Section: Resultsmentioning

confidence: 99%

Binding of the by-product analog benzylsuccinic acid by carboxypeptidase A

Byers¹,

Wolfenden²

1973

Biochemistry

216

108

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“…mp 125.5° ( Eiduson et al, 1950). Hippuryl-i.-/3-phenyl-lactic acid was prepared by treatment of L-/3-phenyllactic acid with 2-phenyl-5-oxazolone according to the method of Kaiser and Carson (1965). Its initial crystallization was carried out in benzene-1,2-dichloroethane.…”

Section: Methodsmentioning

confidence: 99%

The Kinetics of Some Carboxypeptidase A and Acetylcarboxypeptidase A Catalyzed Hydrolyses^*

Whitaker¹,

Menger²,

Bender³

1966

Biochemistry

104

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ABsTRAcr: The kinetic constants, kcst and Kdapp), have been determined for the carboxypeptidase A and acetylcarboxypeptidase A catalyzed hydrolysis of benzyloxycarbonylglycyl-L-phenylalanine, hippuryl-Lphenylalanine, and hippuryl-L-phenyllactic acid. Acetylcarboxypeptidase A was prepared by treatment of carboxypeptidase A with N-acetylimidazole ; the most extensively acetylated enzyme showed 9 % of the activity of the unmodified enzyme on a standard assay using benzyloxycarbonylglycyl-L-phenylalanine. The (major) substrate inhibition seen in the carboxypeptidase A catalyzed hydrolysis of hippuryl-L-&phenyl-lactic acid and the (minor) substrate activation seen in the carboxypeptidase A catalyzed hydrolysis of benzyl-V allee and co-workers have found that various treatments of carboxypeptidase A, such as acylation with carboxylic acid derivatives, photooxidation, iodination, or replacement of the zinc ion of the enzyme by either cadmium or mercury ions, increase the esterase activity of the enzyme, as measured by a standard assay using hippuryl-DL-P-phenyllactic acid or hippuryl-DL-P-indolyllactic acid, but decrease the peptidase activity, as measured by a standard assay using benzyloxycarbonylglycyl-L-phenylalanine or several other peptide substrates Simpson et al., 1963;Riordan and Vallee, 1963; Vallee, 1964a,b;Bethune et al., 1964;Riordan and Vallee, 1964). Thus, chemical modification of carboxypeptidase A leads to particularly intriguing results. It is of interest to examine the modifications of carboxypeptidase A with a view to finding out whether such modifications exert changes in bindings, Kdapp), in the catalytic process, V,,,, or in other factors which affect the rate.A priori, chemical modification of an enzyme such as carboxypeptidase A could manifest itself in a modified rate of hydrolysis through one or more of the following causes. (1) The catalytic rate constant, kcat, could change.(2) The apparent Michaelis constant, K,(app), 386 oxycarbonylglycyl-L-phenylalanine are not observable in the hydrolysis of the substrates by acetylcarboxypeptidase A. With the substrate benzyloxycarbonylglycyl-L-phenylalanine, acetylation of the enzyme decreased k,,, by a factor of two but increased the K,(app) by 15-fold. With the exact structural analogs, hippuryl-L-phenylalanine and hippuryl-L-@-phenyllactic acid, acetylation of the enzyme decreased the kcat of the peptidase reaction 7-fold, whereas the kcat of the esterase reaction went up about 2.5-fold. On the other hand, acetylation of the enzyme increased the K,(app) of the esterase reaction by 40-fold, whereas that for the peptidase reaction did not change. Thus, no clear-cut mechanistic implications may be drawn from these kinetic results. could change.(3) Ki of an inhibitor or substrate could be altered. (4) In a multistep enzymatic process (e.g., if the reaction involved an acyl-enzyme intermediate) the steps could be affected differently; in the extreme case there could be a change in the rate-limiting step.( 5 ) The dependence of active center groups on med...

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“…Inhibitors of the Hydrolysis of BzGlyGlyPhe and CbzGly-Gly-i.-Phe. /3-Phenylpropionate is a competitive inhibitor of the carboxypeptidase-catalyzed hydrolysis of hippuryl-Lmandelate (Kaiser and Carson, 1965). It also inhibits the hydrolysis of hippuryl-/3-DL-phenyllactic acid (Coleman and Vallee, 1964).…”

Section: Hydrolysis Of Tripeptides By Metallocarboxypeptidasesmentioning

confidence: 99%

Kinetics of carboxypeptidase A. II. Inhibitors of the hydrolysis of oligopeptides

Auld¹,

Vallée²

1970

Biochemistry

112

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Inhibition of the esterase action of carboxypeptidase A

Cited by 19 publications

References 7 publications

Binding of the by-product analog benzylsuccinic acid by carboxypeptidase A

Binding of the by-product analog benzylsuccinic acid by carboxypeptidase A

The Kinetics of Some Carboxypeptidase A and Acetylcarboxypeptidase A Catalyzed Hydrolyses^*

Kinetics of carboxypeptidase A. II. Inhibitors of the hydrolysis of oligopeptides

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Inhibition of the esterase action of carboxypeptidase A

Cited by 19 publications

References 7 publications

Binding of the by-product analog benzylsuccinic acid by carboxypeptidase A

Binding of the by-product analog benzylsuccinic acid by carboxypeptidase A

The Kinetics of Some Carboxypeptidase A and Acetylcarboxypeptidase A Catalyzed Hydrolyses*

Kinetics of carboxypeptidase A. II. Inhibitors of the hydrolysis of oligopeptides

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The Kinetics of Some Carboxypeptidase A and Acetylcarboxypeptidase A Catalyzed Hydrolyses^*