TY - JOUR
T1 - In silico design of a mutant of cytochrome P450 containing selenocysteine
AU - Cohen, Shimrit
AU - Kumar, Devesh
AU - Shaik, Sason
PY - 2006/3/1
Y1 - 2006/3/1
N2 - A mutant of P450cam, in which the cysteine ligand was replaced by selenocysteine, was designed theoretically using hybrid QM/MM (quantum mechanical/molecular mechanical) calculations. The calculations of the active species, Se-Cpdl (selenocysteine-Compound I), of the mutant enzyme indicate that SeCpd I will be formed faster than the wild-type species and be consumed more slowly in C-H hydroxylation. As such, our calculations suggest that Se-Cpd I can be observed unlike the elusive species of the wild-type enzyme (Denisov, I. G.; Makris, T. M.; Sugar, S. G.; Schlichting, I. Chem. Rev. 2005, 105, 2253-2277). Spectral features of Se-Cpd I were calculated and may assist such eventual characterization. The observation of Se-Cpd I will resolve the major puzzle in the catalytic cycle of a key enzyme in nature.
AB - A mutant of P450cam, in which the cysteine ligand was replaced by selenocysteine, was designed theoretically using hybrid QM/MM (quantum mechanical/molecular mechanical) calculations. The calculations of the active species, Se-Cpdl (selenocysteine-Compound I), of the mutant enzyme indicate that SeCpd I will be formed faster than the wild-type species and be consumed more slowly in C-H hydroxylation. As such, our calculations suggest that Se-Cpd I can be observed unlike the elusive species of the wild-type enzyme (Denisov, I. G.; Makris, T. M.; Sugar, S. G.; Schlichting, I. Chem. Rev. 2005, 105, 2253-2277). Spectral features of Se-Cpd I were calculated and may assist such eventual characterization. The observation of Se-Cpd I will resolve the major puzzle in the catalytic cycle of a key enzyme in nature.
UR - http://www.scopus.com/inward/record.url?scp=33644648714&partnerID=8YFLogxK
U2 - 10.1021/ja056586c
DO - 10.1021/ja056586c
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C2 - 16492051
AN - SCOPUS:33644648714
SN - 0002-7863
VL - 128
SP - 2649
EP - 2653
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 8
ER -