In silico design of a mutant of cytochrome P450 containing selenocysteine

Shimrit Cohen, Devesh Kumar, Sason Shaik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2649-2653
Number of pages5
JournalJournal of the American Chemical Society
Volume128
Issue number8
DOIs
StatePublished - 1 Mar 2006

Fingerprint

Dive into the research topics of 'In silico design of a mutant of cytochrome P450 containing selenocysteine'. Together they form a unique fingerprint.

Cite this