2011
DOI: 10.1021/ja111657j
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Abstract: A series of computational methods were used to study how cytochrome P450 2A6 (CYP2A6) interacts with (S)-(−)-nicotine, demonstrating that the dominant molecular species of (S)-(−)-nicotine in CYP2A6 active site exists in the free base state (with two conformations, SRt and SRc), despite of the fact that the protonated state is dominant for the free ligand in solution. The computational results reveal that the dominant pathway of nicotine metabolism in CYP2A6 is through nicotine free base oxidation. Further, fi… Show more

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Cited by 111 publications
(93 citation statements)
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“…ab initio, DFT, or semiempirical method) treatment of atoms involved in the active site with a MM description of the native protein environment [135][136][137]. QM/MM approach is becoming increasingly popular for the study of biochemical reactions [138][139][140].…”
Section: Summary and Perspectivementioning
confidence: 99%
“…ab initio, DFT, or semiempirical method) treatment of atoms involved in the active site with a MM description of the native protein environment [135][136][137]. QM/MM approach is becoming increasingly popular for the study of biochemical reactions [138][139][140].…”
Section: Summary and Perspectivementioning
confidence: 99%
“…The mechanism of P450 enzymes, with oxidation mechanisms and inhibition has received particular attention [30][31][32][33][34][35][36]. Plant AOS and related atypical P450s in the prostaglandin H 2 to prostacyclin pathway have also been studied extensively.…”
Section: Introductionmentioning
confidence: 99%
“…[28][29][30][31] The study of solvent e®ect on the stability of isomers indicates, (I)-isomer is still the most stable one among all the isomers. On the other hand, ÁE 1 values decrease and ÁE 2 values increase, as polarity of solvent increase Among the transition states, TSb state changes considerably with polarity of solvent.…”
Section: -2mentioning
confidence: 99%