A mechanism for the transfer of the carboxyl‐group from 1'‐<i>N</i>‐carboxybiotin to acceptor substrates by biotin‐containing enzymes

Goodall, Gregory J.; Prager, R. H.; Wallace, John C.; Keech, D.B.

doi:10.1016/0014-5793(83)81150-8

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…Thus, some characteristic of this enzymic subsite must enhance the tendency of carboxybiotin to be decarboxylated. Goodall et al (1983) attempted to address this problem by proposing a mechanism in which a proton is extracted from N-3 of carboxybiotin by a base in the site of reaction 2. This enhances the nucleophilicity of the ureido oxygen, which can then remove a proton from pyruvate in a reaction similar to that of Retey and Lynen (1965).…”

Section: Discussionmentioning

confidence: 99%

Carbon-13 and deuterium isotope effects on oxalacetate decarboxylation by pyruvate carboxylase

Attwood¹,

Tipton²,

Cleland³

1986

Biochemistry

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Deuterium and 13C isotope effects for the enzymic decarboxylation of oxalacetate showed that both deuterium- and 13C-sensitive steps in the reaction are partially rate limiting. A normal alpha-secondary effect of 1.2 per deuterium was calculated for the reaction in which pyruvate-d3 was the substrate, suggesting that the enolate of pyruvate was an intermediate in the reaction. The large normal alpha-secondary deuterium isotope effect of 1.7 when oxalacetate-d2 was the substrate suggests that the motions of the secondary hydrogens are coupled to that of the primary hydrogen during the protonation of the enolate of pyruvate. The reduction in the magnitude of the 13C isotope effect for the oxamate-dependent decarboxylation of oxalacetate from 1.0238 to 1.0155 when the reaction was performed in D2O (primary deuterum isotope effect = 2.1) clearly indicates that the transfer of the proton and carboxyl group between biotin and pyruvate does not occur via a single concerted reaction. Mechanisms in which biotin is activated to react with CO2 (prior to transfer of the proton on N-1) by bond formation between the sulfur and the ureido carbon, or in which the sequence of events is decarboxylation of oxalacetate, proton transfer from biotin to enolpyruvate, and carboxylation of enolbiotin, predict that the 13C isotope effect in D2O should be substantially lower than the observed value. A stepwise mechanism that does fit the data is one in which a proton is removed from biotin by a sulfhydryl group on the enzyme prior to carboxyl transfer, as long as the sulfhydryl group has an abnormally low pK.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Carbon-13 and deuterium isotope effects on oxalacetate decarboxylation by pyruvate carboxylase

Attwood¹,

Tipton²,

Cleland³

1986

Biochemistry

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“…Biotin preserves a carboxyl group after ATP-dependent carboxylation has occurred, and it readily transfers the carboxyl group to an acceptor. However, biotin is considered to be inherently unreactive, and it must be activated to perform the carboxy transfer reaction …”

Section: Introductionmentioning

confidence: 99%

Theoretical Study of Cooperativity in Biotin

Zhang

et al. 2007

J. Phys. Chem. B

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To give a deeper insight into the widely discussed catalytic mechanism of biotin, four representative model molecules and their aggregates hydrogen bonding (H-bonding) to water molecules were investigated by means of ab initio calculations and compared with molecular dynamics simulations. The roles of the ureido group, the sulfur atom, and the side chain of biotin are examined and discussed, respectively. Some significant H-bonding cooperativities are theoretically demonstrated in the ureido group of biotin. The pi-electron delocalization of the ureido group makes the system a good candidate for the H-bonding cooperativities, which in turn increases the covalent character of the corresponding H-bonds and facilitates the electrophilic substitution of the nitrogen atoms in the ureido group. The sulfur of biotin may participate in the delocalized pi-electron system of the ureido group via special sulfur-nitrogen bonding interactions, which reinforces the H-bonding cooperativities of the ureido group. The side chain of biotin not only reduced the accessibility of 3-NH due to steric hindrance but also enhanced the H-bonding cooperativities of the ureido group by folding over to hydrogen bond to more water molecules. The folded states are a probable way of activating 1-NH by strong cooperative effects. In addition, the H-bonding cooperativities may be a significant reason for the strong and specific binding between biotin and streptavidin.

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“…Wallace, Keech, and co-workers showed that in pyruvate carboxylase, a typical biotin-dependent enzyme, the reactivity of N (1‘)-carboxybiotin is altered once the acceptor substrate (or its analogue) is bound . The mechanism for such activation is unknown although several schemes have been suggested involving structural changes in the protein and cofactor. ,, An alternative utilization of a structural change in a protein is one that leads to specific stabilization of a transition state relative to a reactant through desolvation. , The energy for this desolvation can be derived from coupling of favorable binding interactions between the substrate and the enzyme. Could such a mechanism contribute to increased reactivity of N (1‘)-carboxybiotin upon the binding of substrate?…”

mentioning

confidence: 99%

“…4 The mechanism for such activation is unknown although several schemes have been suggested involving structural changes in the protein and cofactor. 2,5,6 An alternative utilization of a structural change in a protein is one that leads to specific stabilization of a transition state relative to a reactant through desolvation. 7,8 The energy for this desolvation can be derived from coupling of favorable binding interactions between the substrate and the enzyme.…”

mentioning

confidence: 99%

Solvent-Accelerated Decarboxylation of N-Carboxy-2-imidazolidinone. Implications for Stability of Intermediates in Biotin-Dependent Carboxylations

1996

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The decarboxylation of N-carboxy-2-imidazolidinone has previously been established as a model for the transfer of carbon dioxide from N(1‘)-carboxybiotin. The present paper reports the pH-dependence of the reaction as well as the acceleration of the reaction in methanol and in acetonitrile. These results suggest that enzymic reactions of N(1‘)-carboxybiotin in a hydrophobic active site with decreased hydrogen bonding can be rapid if the energy of desolvation is compensated by the energy made available by association of the substrate and protein. In addition, a report on the decarboxylation of N-carboxy-2-imidazolidinone in organic solvents containing macrocycles (Kluger, R.; Tsao, B. J. Am. Chem. Soc. 1993, 115, 2089−90) must be reinterpreted on the basis of the inherent instability of the substrate under the reaction conditions.

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A mechanism for the transfer of the carboxyl‐group from 1'‐N‐carboxybiotin to acceptor substrates by biotin‐containing enzymes

Cited by 10 publications

References 21 publications

Carbon-13 and deuterium isotope effects on oxalacetate decarboxylation by pyruvate carboxylase

Carbon-13 and deuterium isotope effects on oxalacetate decarboxylation by pyruvate carboxylase

Theoretical Study of Cooperativity in Biotin

Solvent-Accelerated Decarboxylation of N-Carboxy-2-imidazolidinone. Implications for Stability of Intermediates in Biotin-Dependent Carboxylations

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