Cytochrome P450OleT (CYP450OleT), a member of CYP450 Peroxygenases, catalyzes unusual decarboxylation activity. Unlike other members of the peroxygenases family, CYP450OleT possesses a Histidine at the 85th position, which was supposed to be the root cause of the decarboxylation activity in CYP450OleT. This work addresses the His85Gln mutant paradox where mutation of HisGln still shows efficient decarboxylation activity in CYP450OleT. The MD simulation of the H85Q mutant of CYP450OleT shows that in the absence of the histidine at 85th position, an Asp239 plays a similar role via a well-organized water channel. Our simulation shows that such a water channel is vital for the optimal substrate positioning needed for the decarboxylation activity and is gated by the Q85-R242 residue pair. Interestingly, the MD simulation of the WT CYP450BSβ shows a closed channel that blocks the access to the Glu236 (analogous residue to Asp239 in CYP450OleT) and, therefore CYP450BSβ shows low decarboxylation activity.
The supporting information contains the QM geometries, reaction profiles and RMSDs during the simulations