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Figure 2
The transition state for the hydroxylation of S-ibuprofen at C3 in the human drug-metabolizing cytochrome P450 2C9 (Lonsdale et al., 2013BB25). The H atom at C3 undergoes abstraction by the ferryl O atom of the porphyrin (shown as a yellow dashed line). Knowledge of the mechanism and transition states for reactions such as these can be useful in the design of new pharmaceutical compounds with desired metabolic properties. The reaction was modelled with QM/MM (using the QoMMMa program; Harvey, 2004BB16) using multiple starting structures taken from MD simulations (performed using CHARMM; Brooks et al., 1983BB5) and the CHARMM27 force field (MacKerell et al., 2000BB29). The QM region is shown in ball-and-stick representation.

Journal logoBIOLOGICAL
ISSN: 1399-0047
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