TY - JOUR
T1 - Decarboxylation and Protonation Enigma in the H85Q Mutant of Cytochrome P450OleT
AU - Yadav, Shalini
AU - Shaik, Sason
AU - Dubey, Kshatresh Dutta
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/4/6
Y1 - 2023/4/6
N2 - 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 His85 → Gln mutant paradox, where mutation of His → Gln 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 the 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-N242 residue pair. Interestingly, the MD simulation of the WT CYP450BSβ shows a closed channel that blocks access to the Glu236 (analogous residue to Asp239 in CYP450OleT), and therefore, CYP450BSβ shows low decarboxylation activity.
AB - 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 His85 → Gln mutant paradox, where mutation of His → Gln 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 the 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-N242 residue pair. Interestingly, the MD simulation of the WT CYP450BSβ shows a closed channel that blocks access to the Glu236 (analogous residue to Asp239 in CYP450OleT), and therefore, CYP450BSβ shows low decarboxylation activity.
UR - http://www.scopus.com/inward/record.url?scp=85151393342&partnerID=8YFLogxK
U2 - 10.1021/acs.jpcb.3c00143
DO - 10.1021/acs.jpcb.3c00143
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C2 - 36959730
AN - SCOPUS:85151393342
SN - 1520-6106
VL - 127
SP - 2927
EP - 2933
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 13
ER -