Mechanism of the Propionyl Carboxylase Reaction

Kaziro, Yoshito; Hass, Louis F.; Boyer, Paul D.; Ochoa, Severo

doi:10.1016/s0021-9258(19)83723-7

Cited by 120 publications

(21 citation statements)

References 19 publications

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“…The methyl ester (5) of cyclic phosphonamide 4 is the intermediate that would result if ureido participation in the hydrolysis of diester 3 occurred by participation of the nitrogen center. The kinetic validity of 5 as an intermediate was ruled out by the finding that its rate of hydrolysis is slower than that of 3.…”

Section: Resultsmentioning

confidence: 99%

“…The product is a colorless, viscous liquid: IR (neat) 1634, 1538 cm-1 (C=0): NMR (CDCI3) 2.81 (3 H, d, Vhh' = 5.5 Hz, NHCH3), 3.03 (3 H, s, CH3), 3.37 (3 H, s, OCH3), 4.70 (2 H, s, CH2), 5.3 (1 H, bs, NH). l-Methoxy-l,3-dioxo-2,4-dimethyl-l-phospha-2,4-diazacyclopentane (Cyclic Phosphonamide Methyl Ester) (5). Compound 5 was prepared from 17 by modification17 of the procedure of Petersen and Reuther.30 To 17 (5.33 g, 0.04 mol) dissolved in 20 mL of benzene was added an equimolar amount of concentrated HC1 (4 mL).…”

Section: Resultsmentioning

confidence: 99%

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Mechanism of urea participation in phosphonate ester hydrolysis. Mechanistic and stereochemical criteria for enzymic formation and reaction of phosphorylated biotin

Kluger¹,

Davis²,

Adawadkar³

1979

J. Am. Chem. Soc.

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The mechanism of participation of a urea group in hydrolysis of a phosphonate ester in acidic solution was investigated. Participation of the oxygen center of the ureido group of 1 and 3 at the phosphonate center is consistent with (1) the high degree of facilitation of ester hydrolysis compared to molecules lacking the adjacent functional group, (2) the observation that species resulting from attack of proximal nitrogen atoms of 1 and 3 are more stable than their precursors, and (3) the observation that acidic, anhydrous media containing alcohols cause rapid transesterification. A detailed mechanistic examination suggests that the participation reaction involves initial formation of a pentacovalent phosphorus intermediate with the ratedetermining step overall being breakdown of the intermediate to expel the leaving alcohol. The potential involvement of Ophosphobiotin in adenosine 5'-triphosphate (ATP) dependent carboxylations in enzymic systems is considered with regard to these results, enzymic results from other laboratories, and stereochemical restrictions. It is concluded that all available experimental evidence is consistent with, but does not require, intermediate formation of O-phosphobiotin. Enzymic carboxylation of O-phosphobiotin, leading to formation of iV-carboxybiotin and phosphate, is considered in terms of the stereochemistry of displacement at the phosphorus center of phosphobiotin. An "adjacent" mechanism, not involving free carboxyphosphate, and an "in-line" mechanism, involving free carboxyphosphate are possible. Reactions not involving O-phosphobiotin are likely to involve "in-line" displacement by bicarbonate at the terminal phosphate residue of ATP, requiring inversion of configuration at phosphorus. Since formation of O-phosphobiotin should occur with inversion at phosphorus, and transfer to bicarbonate with inversion or retention, the route via O-phosphobiotin can account for net inversion or net retention at phosphorus.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Mechanism of urea participation in phosphonate ester hydrolysis. Mechanistic and stereochemical criteria for enzymic formation and reaction of phosphorylated biotin

Kluger¹,

Davis²,

Adawadkar³

1979

J. Am. Chem. Soc.

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“…Climent and Rubio (1986) have shown that biotin does not participate in HCOg'-dependent ATP cleavage for biotin carboxylase from Escherichia coli. Additionally, the experiments of Kaziro et al (1962), using HC18C>3" to investigate the mechanism of propionyl-CoA carboxylase (EC 6.4.1.3), showed that bicarbonate participates directly in the cleavage of the dphosphoryl bond of ATP (eq 7).…”

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confidence: 99%

Isolation of a carboxyphosphate intermediate and the locus of acetyl-CoA action in the pyruvate carboxylase reaction

et al. 1992

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When chicken liver pyruvate carboxylase was incubated with either H14CO3- or gamma-[32P]ATP, a labeled carboxyphospho-enzyme intermediate could be isolated. The complex was catalytically competent, as determined by its subsequent ability to transfer either 14CO2 to pyruvate or 32P to ADP. While the carboxyphospho-enzyme complex was inherently unstable and the stoichiometry of the transfer was variable depending on experimental conditions, both the [14C]carboxyphospho-enzyme and the carboxy[32P]phospho-enzyme had similar half-lives. Acetyl-CoA was shown to be involved in the conversion of the carboxyphospho-enzyme complex to the more stable carboxybiotin-enzyme species, which was consistent with the effects of acetyl-CoA on isotope exchange reactions involving ATP. We were unable to detect the formation of a phosphorylated biotin derivative during the ATP cleavage reaction. In the presence of K+ and at pH 9.5, the acetyl-CoA-independent activity of chicken liver pyruvate carboxylase approached 2% of the acetyl-CoA-stimulated rate, which represents a 30-fold increase on previously reported activity for this enzyme.

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“…From studies on pyruvate and propionyl‐CoA carboxylases as well as carbamoyl phosphate synthetases, it is known that carboxyphosphate is a crucial reaction intermediate generated by ATP dependent phosphorylation of bicarbonate. 58 , 59 , 60 A distinct carboxylate binding site is present in biotin carboxylase (3G8C, 4MV9) where HCO 3 − interacts with Glu, Lys, Asn, Arg 61 , 62 and in (N[5])‐carboxyaminoimidazole ribonucleotide synthase (3V4S), where HCO 3 − is connected to Arg and Lys 63 . In both enzymes the formed carboxyphosphate does not diffuse from the active site but immediately transfers the carboxyl group to an acceptor.…”

Section: Resultsmentioning

confidence: 99%

Catalytic and structural properties of ATP‐dependent caprolactamase from Pseudomonas jessenii

et al. 2021

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Caprolactamase is the first enzyme in the caprolactam degradation pathway of Pseudomonas jessenii. It is composed of two subunits (CapA and CapB) and sequence‐related to other ATP‐dependent enzymes involved in lactam hydrolysis, like 5‐oxoprolinases and hydantoinases. Low sequence similarity also exists with ATP‐dependent acetone‐ and acetophenone carboxylases. The caprolactamase was produced in Escherichia coli, isolated by His‐tag affinity chromatography, and subjected to functional and structural studies. Activity toward caprolactam required ATP and was dependent on the presence of bicarbonate in the assay buffer. The hydrolysis product was identified as 6‐aminocaproic acid. Quantum mechanical modeling indicated that the hydrolysis of caprolactam was highly disfavored (ΔG0'= 23 kJ/mol), which explained the ATP dependence. A crystal structure showed that the enzyme exists as an (αβ)2 tetramer and revealed an ATP‐binding site in CapA and a Zn‐coordinating site in CapB. Mutations in the ATP‐binding site of CapA (D11A and D295A) significantly reduced product formation. Mutants with substitutions in the metal binding site of CapB (D41A, H99A, D101A, and H124A) were inactive and less thermostable than the wild‐type enzyme. These residues proved to be essential for activity and on basis of the experimental findings we propose possible mechanisms for ATP‐dependent lactam hydrolysis.

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Mechanism of the Propionyl Carboxylase Reaction

Cited by 120 publications

References 19 publications

Mechanism of urea participation in phosphonate ester hydrolysis. Mechanistic and stereochemical criteria for enzymic formation and reaction of phosphorylated biotin

Mechanism of urea participation in phosphonate ester hydrolysis. Mechanistic and stereochemical criteria for enzymic formation and reaction of phosphorylated biotin

Isolation of a carboxyphosphate intermediate and the locus of acetyl-CoA action in the pyruvate carboxylase reaction

Catalytic and structural properties of ATP‐dependent caprolactamase from Pseudomonas jessenii

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