A Model for Peroxide Heterolysis
How does peroxide react with a heme peroxidase?
- Here is a model based on observations from several structures (including the dioxygen complex ),
together with stopped flow kinetics performed in collaboration with Jim Erman and
Lidia Vitello.
In the figure, OA and OB of peroxide are represented as red spheres, and
their respective hydrogen atoms are represented as white spheres.
In Panel A , the peroxide molecule has displaced Wat 595,
and is forming a bond with the ferric iron atom.
Proton transfer from OA
to His 52 would be favorable as OA of peroxide approaches
the ferric iron.
The dioxygen complex structure suggests that
Wat 695 (yellow sphere) and Wat 596 (not shown) will be unperturbed.
In Panel B , the proton transfer to His 52 is complete,
and it can be seen that now His 52 is well positioned to re-donate
the proton to OB, as required by a heterolytic mechanism.
The position of OA is stabilized via H- bond
from Trp 51.
In Panel C , the OA-OB bond is broken, and Arg 48 moves in
toward the oxene oxygen bound to the iron, which carries
a formal -2 charge. This movement is seen both in the Laue structure
of Compound I and in the fluoride complex of ferric CcP, suggesting
that small hard anions promote the movement of Arg 48 inward toward the
iron atom.
In Panel D , the newly-created water molecule is forced from
the active site by van der Waals contacts with OA, which is bound at the iron.
The distal structure of CcP is designed to transfer a proton
from O1 to O2 of bound peroxide.
His 52 is critical for this process, and mutation of His 52 -> Leu
decreases the rate of reaction by 5 orders of magnitude.
Click here for abstracts pertaining to the role of
distal His 52
and Arg 48
in the
kinetics of the peroxide reaction.
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