Intramolecular nucleophilic attack on carboxylate by ureide anion. General acid–base catalysis of the alkaline cyclisation of 2,2,3,5-tetramethylhydantoic acid

Blagoeva, Iva B.; Pojarlieff, Ivan G.; Kirby, Anthony J.

doi:10.1039/p29840000745

Cited by 17 publications

(16 citation statements)

References 2 publications

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“…First, model chemical studies have shown that the conjugate base of urea can act as a nucleophile on an ionized carboxyl group with general acid catalysis required to stabilize the dianionic intermediate. 37 Second, the direct attack model for carboxyl transfer is consistent with biotin carboxylase being a member of the ATP-grasp superfamily of enzymes. For instance, in the reaction catalyzed by another member of that superfamily, D-Ala-D-Ala ligase, ATP reacts with the carboxyl group of D-Ala to form an acylphosphate.…”

Section: Discussionmentioning

confidence: 65%

Structural Analysis of Substrate, Reaction Intermediate, and Product Binding in Haemophilus influenzae Biotin Carboxylase

et al. 2015

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Acetyl-CoA carboxylase catalyzes the first and regulated step in fatty acid synthesis. In most Gram-negative and Gram-positive bacteria, the enzyme is composed of three proteins: biotin carboxylase, a biotin carboxyl carrier protein (BCCP), and carboxyltransferase. The reaction mechanism involves two half-reactions with biotin carboxylase catalyzing the ATP-dependent carboxylation of biotin-BCCP in the first reaction. In the second reaction, carboxyltransferase catalyzes the transfer of the carboxyl group from biotin-BCCP to acetyl-CoA to form malonyl-CoA. In this report, high-resolution crystal structures of biotin carboxylase from Haemophilus influenzae were determined with bicarbonate, the ATP analogue AMPPCP; the carboxyphosphate intermediate analogues, phosphonoacetamide and phosphonoformate; the products ADP and phosphate; and the carboxybiotin analogue N1′-methoxycarbonyl biotin methyl ester. The structures have a common theme in that bicarbonate, phosphate, and the methyl ester of the carboxyl group of N1′-methoxycarbonyl biotin methyl ester all bound in the same pocket in the active site of biotin carboxylase and as such utilize the same set of amino acids for binding. This finding suggests a catalytic mechanism for biotin carboxylase in which the binding pocket that binds tetrahedral phosphate also accommodates and stabilizes a tetrahedral dianionic transition state resulting from direct transfer of CO2 from the carboxyphosphate intermediate to biotin.

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Section: Discussionmentioning

confidence: 65%

Structural Analysis of Substrate, Reaction Intermediate, and Product Binding in Haemophilus influenzae Biotin Carboxylase

et al. 2015

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“…Data below pH 7 were obtained in HCl solutions (a H = 0.851[HCl]) 4 or extrapolated to zero buffer concentration. At higher pH values (7)(8)(9)(10) the data refer to 0.02 M buffers (phosphate, TRIS, carbonate and glycine amine): we are confident that the contribution of buffer catalysis is not significant at this concentration. The high pH-region (pH > 11.52) was studied in KOH solutions and the pH taken as 14 ϩ log [OH Ϫ ].…”

Section: Kinetics and Mechanisms Ph-rate Profiles For The Cyclization...mentioning

confidence: 80%

A normal gem-dimethyl effect in the base-catalyzed cyclization of ω-( p-nitrophenyl)hydantoic acids: evidence for hindered proton transfer in the permethylated esters †

Blagoeva

Kirby²,

Kochiyashki

et al. 2000

J. Chem. Soc., Perkin Trans. 2

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The cyclization of hydantoic acids 2-UA and 3-UA -kinetics, solvent kinetic isotope effects (SKIE) and buffer catalysis -were studied in an attempt to explain the disappearance of the gem-dimethyl effect (GDME) in the specific base-catalyzed cyclization of hydantoic esters. pH-Rate profiles for both acids (after correction for ionization and for reversibility at high pH) show two regions of unit slope corresponding to different mechanisms. For 2-UA at high pH and 3-UA at lower pH the mechanism is considered to involve rate-determining attack by the ureido anion on the neutral carboxy group, consistent with the observed inverse SKIE. The normal GDME of 15 provides strong evidence that anomalies observed with the esters do indeed result from steric hindrance to proton transfer. The change to rate determining departure of OH Ϫ with 2-UA is caused at low pH by acid catalysis of the reversion of the tetrahedral intermediate (T Ϫ ) to reactants, while with 3-UA at high pH this takes place through T 2Ϫ . The GDME favours attack on the carboxylate anion but makes ring opening more difficult, thus decreasing acid inhibition. The observed β = 0.44 for general base catalysis of the cyclization of 2-UA is consistent with concerted deprotonation and attack of the ureido group. With 3-UA two simultaneous general base-catalyzed reactions take place: slow deprotonation of the ureido group (β = 1.0) and attack of the ureide anion on the carboxy anion aided by the buffer conjugate acid. The estimated GDME is 2800 for the equilibrium between acid anion and hydantoin, ‡ but only 45 and 15 for catalysis by H 3 O ϩ and OH Ϫ , respectively: both reactions are presumed to go through early transition states.

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“…Yields are generally modest. The substituted starting materials can be prepared by reaction of AAs with isocyanates in good yields [267,268]. 1H-Quinazoline-2,4-diones (91) are also available by ring closure of anthranilamides with phosgene [269].…”

Section: Scheme 37mentioning

confidence: 99%

The Chemistry of Anthranilic Acid

Wiklund¹,

Bergman

2006

COS

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Intramolecular nucleophilic attack on carboxylate by ureide anion. General acid–base catalysis of the alkaline cyclisation of 2,2,3,5-tetramethylhydantoic acid

Cited by 17 publications

References 2 publications

Structural Analysis of Substrate, Reaction Intermediate, and Product Binding in Haemophilus influenzae Biotin Carboxylase

Structural Analysis of Substrate, Reaction Intermediate, and Product Binding in Haemophilus influenzae Biotin Carboxylase

A normal gem-dimethyl effect in the base-catalyzed cyclization of ω-( p-nitrophenyl)hydantoic acids: evidence for hindered proton transfer in the permethylated esters †

The Chemistry of Anthranilic Acid

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