Theoretical investigation of the [1,2]-sigmatropic hydrogen migration in the mechanism of oxidation of 2-aminobenzoyl-CoA by 2-aminobenzoyl-CoA monooxygenase/reductase.
The flavin hydroperoxide at the active site of the mixed-function oxidase 2-aminobenzoyl-CoA monooxygenase/reductase (Azoarcus evansii) transfers an oxygen to the 5-position of the 2-aminobenzoyl-CoA substrate to provide the alkoxide intermediate II(-). Hydrogen migration from C5 to C6 follows this monooxygenation. The nature of the monooxygenation intermediate and plausible competing reactions leading to hydrogen migration have been considered. Ab initio molecular orbital theory has been used to calculate structures and electron distributions in intermediate and transition state structures. Electrostatic potential surface calculations establish that the transition state and product, associated with the C5 to C6 hydrogen transfer, are stabilized by electron distribution to the benzoyl-CoA thioester carbonyl oxygen. This is not so for the transition state and product associated with hydrogen transfer from C5 to C4. The activation energy for the 5, 6-shift is 2.5 kcal/mol lower than that for the 5,4-shift. In addition, the product of the hydrogen 5,6-shift is more stable than is the product of the hydrogen 5,4-shift, by approximately 6 kcal/mol. These results explain why only the shift of hydrogen from C5 to C6 is observed experimentally. Oxygen transfer and hydrogen migration almost coincide in the gas phase (activation energy of approximately 0.6 kcal/mol, equivalent to a single bond vibration). Enzymatic formation of alkoxide II(-) requires its stabilization; thus, the rate constant for its breakdown would be slower than in the gas phase.
Torres
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University of California, Santa Barbara, CA 93106, USA.
Bruice
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TC
D000214:Acyl Coenzyme A / Q000378:metabolism*; D020627:Azoarcus / Q000201:enzymology; D005420:Flavoproteins / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008956:Models, Chemical; D010084:Oxidation-Reduction; D013816:Thermodynamics
C403069:2-aminobenzoyl-coenzyme A; D000214:Acyl Coenzyme A; D005420:Flavoproteins; D006859:Hydrogen; D006899:Mixed Function Oxygenases; C062023:2-aminobenzoyl-CoA monooxygenase-reductase