TY - JOUR
T1 - Oxygen Economy of Cytochrome P450
T2 - What is the Origin of the Mixed Functionality as a Dehydrogenase-Oxidase Enzyme Compared with its Normal Function?
AU - Kumar, Devesh
AU - De Visser, Samuël P.
AU - Shaik, Sason
PY - 2004/4/28
Y1 - 2004/4/28
N2 - The economy of dioxygen consumption by enzymes constitutes a fundamental problem in enzymatic chemistry (ref 1). Sometimes, the enzyme converts ALL the oxygen into water, without affecting the organic substrate, thereby acting as an "oxidase" (ref 1). Other times, the enzyme converts all the oxygen into water and causes desaturation in the substrate, thus exhibiting a mixed function as both "oxidase" and "dehydrogenase" (refs 2-5). The present paper describes density functional calculations demonstrating that the oxidase-dehydrogenase mixed activity occurs from the cationic intermediate species and requires electro-steric inhibition of the rebound process. Furthermore, the calculations reveal that the carbocation is formally nascent from an excited state of the active species of the enzyme (2Cpd I), in which the Fe=O moiety is singlet coupled as in the 1Δg state of dioxygen! Thus, our results resolve an important mechanism and reveal the factors that underlie its observability.
AB - The economy of dioxygen consumption by enzymes constitutes a fundamental problem in enzymatic chemistry (ref 1). Sometimes, the enzyme converts ALL the oxygen into water, without affecting the organic substrate, thereby acting as an "oxidase" (ref 1). Other times, the enzyme converts all the oxygen into water and causes desaturation in the substrate, thus exhibiting a mixed function as both "oxidase" and "dehydrogenase" (refs 2-5). The present paper describes density functional calculations demonstrating that the oxidase-dehydrogenase mixed activity occurs from the cationic intermediate species and requires electro-steric inhibition of the rebound process. Furthermore, the calculations reveal that the carbocation is formally nascent from an excited state of the active species of the enzyme (2Cpd I), in which the Fe=O moiety is singlet coupled as in the 1Δg state of dioxygen! Thus, our results resolve an important mechanism and reveal the factors that underlie its observability.
UR - http://www.scopus.com/inward/record.url?scp=1942521285&partnerID=8YFLogxK
U2 - 10.1021/ja0318737
DO - 10.1021/ja0318737
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C2 - 15099082
AN - SCOPUS:1942521285
SN - 0002-7863
VL - 126
SP - 5072
EP - 5073
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 16
ER -