Computational studies on nonenzymatic and enzymatic pyridoxal phosphate catalyzed decarboxylations of 2-aminoisobutyrate

M. D. Toney

Research output: Contribution to journalArticle

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Abstract

A computational study of nonenzymatic and enzymatic pyridoxal phosphate-catalyzed decarboxylation of 2-aminoisobutyrate (AIB) is presented. Four prototropic isomers of a model aldimine between AIB and 5′-deoxypyridoxal, with acetate interacting with the pyridine nitrogen, were employed in calculations of both gas phase and water model (PM3 and PM3-SM3) decarboxylation reaction paths. Calculations employing the transition state structures obtained for the four isomers allow the demonstration of stereoelectronic effects in transition state stabilization as well as a separation of the contributions of the Schiff base and pyridine ring moieties to this stabilization. The unprotonated Schiff base contribution (∼16 kcal/mol) is larger than that of the pyridine ring even when it is protonated (∼10 kcal/mol), providing an explanation of the catalytic power of pyruvoyl-dependent amino acid decarboxylases. An active site model of dialkylglycine decarboxylase was constructed and validated, and enzymatic decarboxylation reaction paths were calculated. The reaction coordinate is shown to be complex, with proton transfer from Lys272 to the coenzyme C4′ likely simultaneous with Cα-CO2 - bond cleavage. The proposed concerted decarboxylation/proton-transfer mechanism provides a simple explanation for the observed specificity of this enzyme toward oxidative decarboxylation.

Original languageEnglish (US)
Pages (from-to)1378-1384
Number of pages7
JournalBiochemistry
Volume40
Issue number5
DOIs
StatePublished - Feb 6 2001

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Decarboxylation
Pyridoxal Phosphate
2,2-dialkylglycine decarboxylase
Proton transfer
Schiff Bases
Isomers
Protons
Stabilization
Carboxy-Lyases
Coenzymes
Catalytic Domain
Acetates
Nitrogen
Demonstrations
Gases
Amino Acids
Water
Enzymes
pyridine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Computational studies on nonenzymatic and enzymatic pyridoxal phosphate catalyzed decarboxylations of 2-aminoisobutyrate. / Toney, M. D.

In: Biochemistry, Vol. 40, No. 5, 06.02.2001, p. 1378-1384.

Research output: Contribution to journalArticle

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