Tryptophan-mediated charge-resonance stabilization in the bis -Fe(IV) redox state of MauG

Abstract

The diheme enzyme MauG catalyzes posttranslational modifications of a methylamine dehydrogenase precursor protein to generate a tryptophan tryptophylquinone cofactor. The MauG-catalyzed reaction proceeds via a bis -Fe(IV) intermediate in which one heme is present as Fe(IV)=O and the other as Fe(IV) with axial histidine and tyrosine ligation. Herein, a unique near-infrared absorption feature exhibited specifically in bis -Fe(IV) MauG is described, and evidence is presented that it results from a charge-resonance-transition phenomenon. As the two hemes are physically separated by 14.5 Å, a hole-hopping mechanism is proposed in which a tryptophan residue located between the hemes is reversibly oxidized and reduced to increase the effective electronic coupling element and enhance the rate of reversible electron transfer between the hemes in bis -Fe(IV) MauG. Analysis of the MauG structure reveals that electron transfer via this mechanism is rapid enough to enable a charge-resonance stabilization of the bis -Fe(IV) state without direct contact between the hemes. The finding of the charge-resonance-transition phenomenon explains why the bis -Fe(IV) intermediate is stabilized in MauG and does not permanently oxidize its own aromatic residues.

Mutation of Trp93 of MauG to tyrosine causes loss of bound Ca2+ and alters the kinetic mechanism of tryptophan tryptophylquinone cofactor biosynthesis

“…This redox state is generated and stabilized by MauG despite the fact that the two haem irons are separated by 21 Å (1 Å = 0.1 nm) (Figure 2A). This stabilization is achieved through an unusual charge-resonance transition in which the two Fe IV haems and Trp 93 , which resides between the two haems, share spin and charge via ultrafast hopping-mediated ET (electron transfer) [16].…”

Could tyrosine and tryptophan serve multiple roles in biological redox processes?

“…It is well established that multi-step tunnelling, called hopping, is required for functional charge transport in many redox enzymes (examples include ribonucleotide reductase [1][2][3][4][5][6][7][8][9], photosystem II [10][11][12], DNA photolyase [13][14][15][16][17][18][19][20][21], MauG [22][23][24][25] and cytochrome c peroxidase [26,27]). Here, we advance the hypothesis that many such enzymes, most especially those that generate high-potential intermediates during turnover, could be irreversibly damaged if the intermediates are not inactivated in some way.…”

Roles of multiple-proton transfer pathways and proton-coupled electron transfer in the reactivity of the bis -Fe IV state of MauG

“…One observes a decrease in intensity and shift of the Soret peak from 406 to 408 nm and appearance of minor peaks at 526 and 559 nm (Fig. 2) (9,12).…”

“…This spectral feature is characteristic of a charge-resonance (CR) transition phenomenon (6,9). A model was presented in which the CR occurs in the absence of direct heme-heme contact by ultrafast and reversible ET between the two high-valent hemes, via hopping through the intervening Trp93 residue (9). In this model the high-valent form of MauG comprises an ensemble of resonance structures including compound ES-like and compound I-like forms of the hemes, with the bis-Fe IV as the dominant species.…”

“…An intervening residue, Trp93, "connects" the two hemes ( Fig. 1) via rapid electron transfer (ET) (6)(7)(8)(9). A unique feature of MauG is that the oxidation of diferric MauG by H 2 O 2 , or of diferrous MauG by O 2 , generates a high-valent bis-Fe IV state (8) in which the high-spin heme is present as Fe IV =O with the His35 ligand, and the other heme is present as Fe IV with the His-Tyr axial ligation retained (5,10,11).…”