Binding‐catalysis relationship in α‐chymotrypsin action as revealed from reversible inhibition study of phenylalkylboronic acids

Antonov, V.K.; Ivanina, Tatiana; Ivanova, Anna G.; Березин, И.В.; Levashov, A. V.; Martínek, Karel

doi:10.1016/0014-5793(72)80011-5

Cited by 22 publications

(13 citation statements)

References 10 publications

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“…Aliphatic and aromatic boronic acids are known to be inhibitors of serine hydrolases (Philipp and Bender, 1971; Antonov et al , 1972). The lipases were also nearly inhibited by phenylboronic acids (10 m M ), The mechanism mainly involves blocking of the active site of the enzyme and inhibition via interaction with the lipase‐active site, which is the serine residue (Garner, 1980).…”

Section: Resultsmentioning

confidence: 99%

Ionic‐Liquid‐Grafted Rigid Poly(p‐Phenylene) Microspheres: Efficient Heterogeneous Media for Metal Scavenging and Catalysis

Li¹,

Wang²,

Kou³

et al. 2010

Chemistry A European J

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Novel guanidinium ionic liquid-grafted rigid poly(p-phenylene) (PPPIL) microspheres have been developed for metal scavenging and catalysis. The noble-metal nanoparticles supported on the microspheres surface can be used as efficient heterogeneous catalysts. The combination of nanoparticles and ionic liquid fragments on the microsphere surfaces enhance the activity and durability of the catalyst. The PPPILPd(0) catalyst has been tested in the Suzuki cross-coupling reaction, and exhibits much higher catalytic activity than Pd catalysts supported on porous polymer matrices. The PPPILPd(0) catalyst can be recycled at least for nine runs without any significant loss of activity. The present approach may, therefore, have potential applications in transition-metal-nanocatalyzed reactions.

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Section: Resultsmentioning

confidence: 99%

Ionic‐Liquid‐Grafted Rigid Poly(p‐Phenylene) Microspheres: Efficient Heterogeneous Media for Metal Scavenging and Catalysis

Li¹,

Wang²,

Kou³

et al. 2010

Chemistry A European J

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“…It is interesting to note that in a recent study (44) of the reversible inhibition of chymotrypsin by alkyl-and w-phenylalkyl-boronic acids, a difference between aliphatic acids and phenyl substituted acids was observed. Here, however, based upon their hydrophobic character as expressed by n-values, the acids containing aromatic rings were more effective inhibitors than their aliphatic counterparts.…”

Section: Discussionmentioning

confidence: 99%

Reversible Inhibition of the Esterase Activity of Carboxypeptidase A by Carboxylate Anions

Bunting¹,

Myers²

1973

Can. J. Chem.

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Reversible inhibition of the hydrolysis of 0-(hippury1)-L-3-phenyllactic acid by carboxypeptidase A has been studied for 26 carboxylate ion ~nhibitors at 25", p H 7.5, and ionic strength 0.2 (NaCI). Competitive inhibition, partially competitive inhibition, and mixed inhibition kinetics were observed. Within homologous series, strictly competitive inhibition by the lower members gave way to partially competitive inhibition with higher members, while homologs having very large hydrocarbon moieties displayed mixed inhibition kinetics. Partially competitive Inhibition in this system is not consistent with a scheme involving only 1:l enzyme-inhibitor complexes; rather, higher order enzyme-inhibitor complexes will be necessary for a complete description of the inhibition mechanism.Inhibition constants (log K i ) for the aliphatic carboxylate ions which are strictly competitive inhibitors, are closely correlated linearly with Hansch's n-parameter for hydrophobicity. This qrrantitatively confirms the importance of hydrophobic interactions between carboxypeptidase A and inhibiting ions. Carboxylate ions containing aromatlc rings are less effective inhibitors than expected on the basis of the n-parameters of their hydrocarbon moieties. The dependence of IogK, on n i n this system is unusually strong for a binding phenomenon, and suggests that an inhibitor-dependent conformational change may also be ~nvolved. ILes constantes d'inhibition (log K i ) pour les ions carboxylate aliphatique lesquels sont des inhibiteurs seulement d e compttition, sont relikes intimement de f a~o n IinCaire avec le paramktre-n de Hansch e n c e i qui a t r a~t a I'hydrophobie. Ce fait confirme qnat~titativetnent I'importance d'lnteractions hydrophobes entre la carboxypeptidase A et les ions responsables de I'inhibition beaucoup moins efficaces qu'il Ctait I prCvisible en se basant sur les parametres-7i d e leur entit6 hydrocarbure. L a relation entre le log K, e t n dans c e systeme, est forte c e qui est inhabituel pour unphCnomkne d e fixationet suggkre ainsiqu'un changement conformationnel reliC B I'inhibiteur peut ainsi &tre impliquC.[Traduit par le journal]Can. J. Chem., 51, 2639Chem., 51, (1973 Both the peptidase and esterase activities of other hand, both competitive and non-comcarboxypeptidase A are well-known to be revers-petitive inhibition kinetics have been observed for ibly inhibited by carboxylate anions (1-9). the same inhibitor against different peptide Systematic studies on the dependence of the substrates. Furthermore, inhibition of peptidase nature and extent of this inhibition on the struc-activity by 3-phenylpropanoate (hydrocinture of the inhibiting anion are lacking, however. namate) ion has been suggested to be a mixture A systematic study is particularly important in of competitive, non-competitive, and mixed the light of the variety of inhibition mechanisms inhibitory modes (1 1 can only be considered to be "apparent" conCan. J. Chem. Downloaded from www.nrcresearchpress.com by 54.245.13.81 on 05/11/18For personal us...

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“…It is beyond doubt that the acceleration of the catalytic steps observed as the hydrophobicity of the substrate molecule rises [equation ( 8 ) ] is due to the forces of sorption of the substrate on the enzyme. A bindingcatalysis relationship in a-chymotrypsin action has been previously discussed [1,2,23,31]. Now we would like to point out that in the series of substrates studied this relationship is described by the approximate equation (9) AAG, = A A G~+ = A A G~* which follows from eqs.…”

Section: Aag3* Aagtranscr)mentioning

confidence: 79%

The free energy–reaction coordinate profile for α‐chymotryptic hydrolysis of a series of N‐acetyl‐α‐L‐amino acid methyl esters

Martínek¹,

Klyosov²,

Kazanskaya³

et al. 1974

Int J of Chemical Kinetics

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The effect of added nucleophiles (methanol and 1,4-butanediol) on the steady-state kinetics of a-chymotryptic hydrolysis of a series of -V-acetyl-L-amino acid methyl esters, R-CH(NHCOCH3)C(O)OCH3, has been studied. As a result, the rate and equilibrium consta.nts of the "elementary" steps of the enzyme process have been determined.It has also been demonstrated how the free energy-reaction coordinate profile changes if the structure (the size of the hydrocarbon chain) of the "chemically inert" substrate fragment R is varied. The effects observed can be described by the following equation:where A G~ and AGa are the free energies of formation of metastable intermediates, i.e., the enzyme-substrate complex and the acylenzyme, respectively, aGz* and aG3* are the free energies of activation for the chemical steps, i.e., enzyme acylation and acylenzyme hydrolysis, respec'ively; and AGt,,,,(R) is the free energy of transfer of substrate group R from water into a nonaqueous solvent.To explain the results obtained, a mechanism for enzyme-substrate interaction is suggested according to which the potential free energy of sorption of substrate group R on the enzyme is 2 AGtra,,(R). Such a high gain in the free energy of hydrophobic interaction may only be realized if (a) in the free enzyme the sorption region has a thermodynamically unfavorable contact with the aqueous medium, and (b) water is forced out of the active center as a result of the hydrophobic interaction of substrate group R with the enzyme.Such a model is in agreement with the published x-ray data on the structure of the crystalline enzyme.The kinetic experiment has proved that not all the potential free energy of sorption is realized as binding force. Thus the true free energy of the binding of substrate group R with tne protein does not exceed half the maximum value, both in the enzyme-substrate complex and acylenzyme.

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Binding‐catalysis relationship in α‐chymotrypsin action as revealed from reversible inhibition study of phenylalkylboronic acids

Cited by 22 publications

References 10 publications

Ionic‐Liquid‐Grafted Rigid Poly(p‐Phenylene) Microspheres: Efficient Heterogeneous Media for Metal Scavenging and Catalysis

Ionic‐Liquid‐Grafted Rigid Poly(p‐Phenylene) Microspheres: Efficient Heterogeneous Media for Metal Scavenging and Catalysis

Reversible Inhibition of the Esterase Activity of Carboxypeptidase A by Carboxylate Anions

The free energy–reaction coordinate profile for α‐chymotryptic hydrolysis of a series of N‐acetyl‐α‐L‐amino acid methyl esters

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