Biochemical Pharmacology

Baillie, A. C.; Wright, Kirsten M.

doi:10.1016/b978-0-08-030812-8.50013-7

Cited by 4 publications

(2 citation statements)

References 176 publications

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“…Synthesis of AcPhi. was conducted according to the procedure reported by Baillie et al 15 PrPhi was prepared as described previously. 16 Methyl acetylphosphonate (MAP) was synthesized using trimethylphosphite and acetylchloride as reagents according to the method of Kluger et al 17 Purity and correct synthesis of all compounds were confirmed by NMR spectroscopy and mass spectrometry.…”

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confidence: 99%

Glyoxylate Carboligase: A Unique Thiamin Diphosphate-Dependent Enzyme That Can Cycle between the 4′-Aminopyrimidinium and 1′,4′-Iminopyrimidine Tautomeric Forms in the Absence of the Conserved Glutamate

et al. 2012

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Glyoxylate carboligase (GCL) is a thiamin diphosphate (ThDP)-dependent enzyme, which catalyzes the decarboxylation of glyoxylate and ligation to a second molecule of glyoxylate to form tartronate semialdehyde (TSA). This enzyme is unique among ThDP enzymes in that it lacks a conserved glutamate near the N1′ atom of ThDP (replaced by Val51), or any other potential acid-base side chains near ThDP. The V51D substitution shifts the pH optimum to 6.0-6.2 (pKa of 6.2) for TSA formation from pH 7.0-7.7 in wild type GCL. This pKa is similar to the pKa of 6.1 for the [1′,4′-iminopyrimidine (IP)]/[4′-aminopyrimidinium (APH+)] protonic equilibrium, suggesting that the same group(s) control both ThDP protonation and TSA formation. The key covalent ThDP-bound intermediates were identified on V51D GCL by a combination of steady-state and stopped-flow circular dichroism methods, yielding rate constants for their formation and decomposition. It was demonstrated that active center variants with substitution at I393 could synthesize (S)-acetolactate from pyruvate solely, and acetylglycolate derived from pyruvate as acetyl donor and glyoxylate as acceptor, implying that this substitutent favored pyruvate as donor in carboligase reactions. Consistent with these observations, the I393A GLC variants could stabilize the pre-decarboxylation intermediate analogs derived from acetylphosphinate, propionylphosphinate and methyl acetylphosphonate in their IP tautomeric forms notwithstanding the absence of the conserved glutamate. The role of the residue at the position occupied typically by the conserved Glu controls the pH dependence of kinetic parameters, while the entire reaction sequence could be catalyzed by ThDP itself, once the APH+ form is accessible.

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confidence: 99%

Glyoxylate Carboligase: A Unique Thiamin Diphosphate-Dependent Enzyme That Can Cycle between the 4′-Aminopyrimidinium and 1′,4′-Iminopyrimidine Tautomeric Forms in the Absence of the Conserved Glutamate

et al. 2012

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“…Insects treated with polychlorocycloalkane insecticides develop violent quivering of the body followed by convulsions and paral-ysis, symptoms consistent with an effect on the nervous system (99). One putative site of action of dieldrin is considered to be the presynaptic terminals of cholinergic junctions (100).…”

Section: Insecticidesmentioning

confidence: 99%