Geometric and electronic structures of the His–Fe(IV)=O and His–Fe(IV)–Tyr hemes of MauG

Proc. Natl. Acad. Sci. U.S.A.

et al. 2013

Self Cite

102

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.

Section: Resultssupporting

confidence: 90%

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

Geng

Dornevil

Proc. Natl. Acad. Sci. U.S.A.

et al. 2013

Self Cite

102

“…Tyrosine is relatively rare as a heme ligand, and this is the first example involving a c -type heme. This heme is more sequestered from solvent than the high-spin heme, and spectroscopic studies are consistent with retention of the His-Tyr ligation in all three MauG redox states (21, 36, 37, 40). At the MauG domain interface between the hemes lies a conserved tryptophan (Trp93).…”

Section: Structure-function Studies Of Maug and Premadhsupporting

confidence: 58%

“…X-ray absorption spectroscopy of H 2 O 2 treated MauG coupled to density functional theory modeling demonstrated that the high-spin heme is the site of the Fe(IV)=O in bis -Fe(IV) MauG (40). This is also consistent with electron density observed in H 2 O 2 treated MauG-preMADH crystals (39).…”

Section: Structure-function Studies Of Maug and Premadhmentioning

confidence: 99%

Posttranslational Biosynthesis of the Protein-Derived Cofactor Tryptophan Tryptophylquinone

Wilmot²

2013

Annu. Rev. Biochem.

Self Cite

Methylamine dehydrogenase (MADH) catalyzes the oxidative deamination of methylamine to formaldehyde and ammonia. Tryptophan tryptophylquinone (TTQ) is the protein-derived cofactor of MADH that is required for these catalytic activities. TTQ is biosynthesized through the post-translational modification of two Trp residues within MADH, during which the indole rings of two Trp side chains are cross-linked and two oxygen atoms are inserted into one of the indole rings. MauG is a c-type diheme enzyme that catalyzes the final three reactions in TTQ formation. In total, this is a six-electron oxidation process requiring three cycles of MauG-dependent two-electron oxidation events using either H2O2 or O2. The MauG redox form that is responsible for the catalytic activity is an unprecedented bis-Fe(IV) species. The amino acids of MADH that are modified are ~ 40 Å from the site where MauG binds oxygen, and the reaction proceeds by a hole hopping electron transfer mechanism. This review will address these highly unusual aspects of the long range catalytic reaction that is mediated by MauG.

“…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). Formation of the bis-Fe IV state is accompanied by changes in the visible absorbance spectrum.…”

mentioning

confidence: 99%

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

Williamson

Proc. Natl. Acad. Sci. U.S.A.

2015

Self Cite

The high-valent state of the diheme enzyme MauG exhibits charge–resonance (CR) stabilization in which the major species is a bis-FeIV state with one heme present as FeIV=O and the other as FeIV with axial heme ligands provided by His and Tyr side chains. In the absence of its substrate, the high-valent state is relatively stable and returns to the diferric state over several minutes. It is shown that this process occurs in two phases. The first phase is redistribution of the resonance species that support the CR. The second phase is the loss of CR and reduction to the diferric state. Thermodynamic analysis revealed that the rates of the two phases exhibited different temperature dependencies and activation energies of 8.9 and 19.6 kcal/mol. The two phases exhibited kinetic solvent isotope effects of 2.5 and 2.3. Proton inventory plots of each reaction phase exhibited extreme curvature that could not be fit to models for one- or multiple-proton transfers in the transition state. Each did fit well to a model for two alternative pathways for proton transfer, each involving multiple protons. In each case the experimentally determined fractionation factors were consistent with one of the pathways involving tunneling. The percent of the reaction that involved the tunneling pathway differed for the two reaction phases. Using the crystal structure of MauG it was possible to propose proton–transfer pathways consistent with the experimental data using water molecules and amino acid side chains in the distal pocket of the high-spin heme.