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Proton Relay Network in P450cam is Formed Upon Docking of its Redox Partner Putidaredoxin (Pdx)

submitted on 28.01.2019 and posted on 29.01.2019 by Ilke Ugur Marion, Prasanna Chandrasekhar
Cytochromes P450 are versatile heme-based enzymes responsible for vital life processes. Of these, P450cam (substrate camphor) has been most studied. Despite this, precise mechanisms of the key O-O cleavage step remain elusive to date; effects observed in various enzyme mutants remain unexplained. We have carried out extended (up to 1000 ns) MM-MD and follow-on QM/MM computations, both on the well-studied FeOO state and, for the first time, on Cpd(0). Our simulations include (all camphor-bound) : (1) WT (wild type), FeOO state. (2) WT, Cpd(0). (3) Pdx-docked-WT, FeOO state. (4) Pdx-docked WT, Cpd(0). (5) Pdx-docked T252A mutant, Cpd(0). Among our key findings, for the first time to our knowledge: (1) Effect of Pdx docking goes far beyond that indicated in prior studies: it leads to specific alterations in secondary structure that create the crucial proton relay network. (2) The specific proton relay networks we identify are FeOO(H)---T252---nH2O---D251 in WT and FeOO(H)---nH2O---D251 in T252A mutant; both occur with Pdx docking. (3) Direct interaction of D251 with -FeOOH is, respectively, rare/frequent in WT/T252A mutant. (4) T252 is in the proton relay network. (5) Positioning of camphor is crucial: when camphor is part of H-bonding network, coupling is facilitated.


Ashwin-Ushas Corporation


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Ashwin-Ushas Corporation



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Declaration of Conflict of Interest

No conflict of interest

Version Notes

DRAFT2 2019-01-28