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BBA - Proteins and Proteomics (v.1824, #11)
Adenosylcobalamin enzymes: Theory and experiment begin to converge by E. Neil G. Marsh; Melendez Gabriel D. Román Meléndez (pp. 1154-1164).
Adenosylcobalamin (coenzyme B12) serves as the cofactor for a group of enzymes that catalyze unusual rearrangement or elimination reactions. The role of the cofactor as the initiator of reactive free radicals needed for these reactions is well established. Less clear is how these enzymes activate the coenzyme towards homolysis and control the radicals once generated. The availability of high resolution X-ray structures combined with detailed kinetic and spectroscopic analyses have allowed several adenosylcobalamin enzymes to be computationally modeled in some detail. Computer simulations have generally obtained good agreement with experimental data and provided valuable insight into the mechanisms of these unusual reactions. Importantly, atomistic modeling of the enzymes has allowed the role of specific interactions between protein, substrate and coenzyme to be explored, leading to mechanistic predictions that can now be tested experimentally. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► AdoCbl-dependent enzymes catalyze unusual rearrangement and elimination reactions. ► Experiments point to profound stabilization of radical intermediates by the protein. ► Recent computational modeling informs mechanistic understanding of these enzymes.
Keywords: Coenzyme B; 12; Free radical; Enzyme mechanism
Enzyme catalyzed formation of radicals from S-adenosylmethionine and inhibition of enzyme activity by the cleavage products by Martyn J. Hiscox; Rebecca C. Driesener; Peter L. Roach (pp. 1165-1177).
A large superfamily of enzymes have been identified that make use of radical intermediates derived by reductive cleavage of S-adenosylmethionine. The primary nature of the radical intermediates makes them highly reactive and potent oxidants. They are used to initiate biotransformations by hydrogen atom abstraction, a process that allows a particularly diverse range of substrates to be functionalized, including substrates with relatively inert chemical structures. In the first part of this review, we discuss the evidence supporting the mechanism of radical formation from S-adenosylmethionine. In the second part of the review, we examine the potential of reaction products arising from S-adenosylmethionine to cause product inhibition. The effects of this product inhibition on kinetic studies of ‘radical S-adenosylmethionine’ enzymes are discussed and strategies to overcome these issues are reviewed. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► Alternative SAM cleavage pathways. ► SAM cleavage products and product-like molecules may be inhibitory. ► Product inhibition of radical SAM enzymes can be relieved by MTAN. ► Substrate binding lowers the energetic barrier to radical formation.
Keywords: Abbreviations; SAM; S; -adenosylmethionine; DOA; •; 5′-deoxyadenosine radical; MTA; 5′-methylthioadenosine; ACP; •; 3-amino-3-carboxypropyl radical; GRE; glycyl radical enzyme; XAS; X-ray absorption spectroscopy; PLP; 5′-pyridoxal phosphate; DTB; dethiobiotin; SAH; S; -adenosylhomocysteineRadical enzyme mechanism; Radical SAM; Product inhibition; 5′-Deoxyadenosine; 3-Amino-3-carboxypropane; 5′-Methylthioadenosine
Structural diversity in the AdoMet radical enzyme superfamily by Daniel P. Dowling; Jessica L. Vey; Anna K. Croft; Catherine L. Drennan (pp. 1178-1195).
AdoMet radical enzymes are involved in processes such as cofactor biosynthesis, anaerobic metabolism, and natural product biosynthesis. These enzymes utilize the reductive cleavage of S-adenosylmethionine (AdoMet) to affordl-methionine and a transient 5′-deoxyadenosyl radical, which subsequently generates a substrate radical species. By harnessing radical reactivity, the AdoMet radical enzyme superfamily is responsible for an incredible diversity of chemical transformations. Structural analysis reveals that family members adopt a full or partial Triose-phosphate Isomerase Mutase (TIM) barrel protein fold, containing core motifs responsible for binding a catalytic [4Fe–4S] cluster and AdoMet. Here we evaluate over twenty structures of AdoMet radical enzymes and classify them into two categories: ‘traditional’ and ‘ThiC-like’ (named for the structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase (ThiC)). In light of new structural data, we reexamine the ‘traditional’ structural motifs responsible for binding the [4Fe–4S] cluster and AdoMet, and compare and contrast these motifs with the ThiC case. We also review how structural data combine with biochemical, spectroscopic, and computational data to help us understand key features of this enzyme superfamily, such as the energetics, the triggering, and the molecular mechanisms of AdoMet reductive cleavage. This article is part of a Special Issue entitled: Radical SAM Enzymes and Radical Enzymology.► Structural motifs for AdoMet radical enzymes are re-examined. ► Structures are classified into two categories: traditional and ThiC-like. ► Recent insights into function through structure are reviewed.
Keywords: Adenosylmethionine; Iron–sulfur cluster; Adenosylcobalamin; Glycyl radical enzyme; SAM radical
Identification and function of auxiliary iron–sulfur clusters in radical SAM enzymes by Nicholas D. Lanz; Squire J. Booker (pp. 1196-1212).
Radical SAM (RS) enzymes use a 5′-deoxyadenosyl 5′-radical generated from a reductive cleavage of S-adenosyl-l-methionine to catalyze over 40 distinct reaction types. A distinguishing feature of these enzymes is a [4Fe–4S] cluster to which each of three iron ions is ligated by three cysteinyl residues most often located in a Cx3Cx2C motif. The α-amino and α-carboxylate groups of SAM anchor the molecule to the remaining iron ion, which presumably facilitates its reductive cleavage. A subset of RS enzymes contains additional iron–sulfur clusters, – which we term auxiliary clusters – most of which have unidentified functions. Enzymes in this subset are involved in cofactor biosynthesis and maturation, post-transcriptional and post-translational modification, enzyme activation, and antibiotic biosynthesis. The additional clusters in these enzymes have been proposed to function in sulfur donation, electron transfer, and substrate anchoring. This review will highlight evidence supporting the presence of multiple iron–sulfur clusters in these enzymes as well as their predicted roles in catalysis. This article is part of a special issue entitled: Radical SAM enzymes and radical enzymology.► Auxiliary Fe/S clusters in RS enzymes that catalyze sulfur insertion are cannibalized during turnover. ► Auxiliary Fe/S clusters can bind in contact with substrates. ► PqqE and other related RS enzymes are members of a larger subclass involved in peptide maturation. ► Some GREs and RS anSMEs contain three [4Fe–4S] clusters per polypeptide. ► AlbA uses RS chemistry to catalyze a reaction similar to that of isopenicillin N-synthase.
Keywords: Radical SAM; Iron–sulfur cluster; S; -adenosylmethionine; 5′-Deoxyadenosine; Glycyl radical; Radical-dependent post-translational modification
Biotin synthase: Insights into radical-mediated carbon–sulfur bond formation by Corey J. Fugate; Joseph T. Jarrett (pp. 1213-1222).
The enzyme cofactor and essential vitamin biotin is biosynthesized in bacteria, fungi, and plants through a pathway that culminates with the addition of a sulfur atom to generate the five-membered thiophane ring. The immediate precursor, dethiobiotin, has methylene and methyl groups at the C6 and C9 positions, respectively, and formation of a thioether bridging these carbon atoms requires cleavage of unactivated CH bonds. Biotin synthase is an S-adenosyl-l-methionine (SAM or AdoMet) radical enzyme that catalyzes reduction of the AdoMet sulfonium to produce 5′-deoxyadenosyl radicals, high-energy carbon radicals that can directly abstract hydrogen atoms from dethiobiotin. The available experimental and structural data suggest that a [2Fe–2S]2+ cluster bound deep within biotin synthase provides a sulfur atom that is added to dethiobiotin in a stepwise reaction, first at the C9 position to generate 9-mercaptodethiobiotin, and then at the C6 position to close the thiophane ring. The formation of sulfur-containing biomolecules through a radical reaction involving an iron–sulfur cluster is an unprecedented reaction in biochemistry; however, recent enzyme discoveries suggest that radical sulfur insertion reactions may be a distinct subgroup within the burgeoning Radical SAM superfamily. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► The biotin biosynthetic pathway ends with insertion of a sulfur atom. ► Biotin synthase contains two iron-sulfur clusters and is an AdoMet radical enzyme. ► A [2Fe-2S]2+ cluster serves as the sulfur donor for the catalytic reaction. ► 9-Mercaptodethiobiotin and a [2Fe-2S]+ cluster are intermediates in catalysis. ► Biotin synthase is half-site active and exhibits slow burst kinetics.
Keywords: Abbreviations; ACP; acyl carrier protein; AdoHcy; S; -adenosyl-; l; -homocysteine; AdoMet; S; -adenosyl-; l; -methionine; AON; 8-amino-7-oxononanoate; CoA; coenzyme A; DAPA; 7,8-diaminopelargonic acid; DAPA; 7,8-diaminopelargonic acid; DTB; dethiobiotin or 5-methyl-2-oxo-4-imidazolidinehexanoic acid; ENDOR; electron-nuclear double resonance; EPR; electron paramagnetic resonance; ESEEM; electron spin echo envelope modulation; 9-MDTB; 9-mercaptodethiobiotin; MTAN; 5′-methylthioadenosine/AdoHcy/5′-dAH nucleosidase; PLP; pyridoxal phosphateEnzyme mechanism; Radical enzyme; Iron-sulfur cluster; Biotin biosynthesis; Cofactor biosynthesis
The methylthiolation reaction mediated by the Radical-SAM enzymes by Mohamed Atta; Simon Arragain; Marc Fontecave; Etienne Mulliez; John F. Hunt; Jon D. Luff; Farhad Forouhar (pp. 1223-1230).
Over the past 10years, considerable progress has been made in our understanding of the mechanistic enzymology of the Radical-SAM enzymes. It is now clear that these enzymes appear to be involved in a remarkably wide range of chemically challenging reactions. This review article highlights mechanistic and structural aspects of the methylthiotransferases (MTTases) sub-class of the Radical-SAM enzymes. The mechanism of methylthio insertion, now observed to be performed by three different enzymes is an exciting unsolved problem. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► Activation of the CH bonds is intricately linked to the presence of a metal ion. ► SAM-dependent radical-based modification of biological macromolecules. ► The methylthiolation reaction mediated by the Radical-SAM enzymes. ► Phylogenetic and sequence analysis of the MTTase family. ► Structural organization of MTTase enzymes.
Keywords: Iron–sulfur cluster; Radical-SAM; tRNA; Methylthiotransferase; Ribosomal S12 protein
Radical SAM enzymes in the biosynthesis of sugar-containing natural products by Mark W. Ruszczycky; Yasushi Ogasawara; Hung-wen Liu (pp. 1231-1244).
Carbohydrates play a key role in the biological activity of numerous natural products. In many instances their biosynthesis requires radical mediated rearrangements, some of which are catalyzed by radical SAM enzymes. BtrN is one such enzyme responsible for the dehydrogenation of a secondary alcohol in the biosynthesis of 2-deoxystreptamine. DesII is another example that catalyzes a deamination reaction necessary for the net C4 deoxygenation of a glucose derivative en route to desosamine formation. BtrN and DesII represent the two most extensively characterized radical SAM enzymes involved in carbohydrate biosynthesis. In this review, we summarize the biosynthetic roles of these two enzymes, their mechanisms of catalysis, the questions that have arisen during these investigations and the insight they can offer for furthering our understanding of radical SAM enzymology. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.Display Omitted► BtrN is a radical SAM enzyme involved in the biosynthesis of 2-deoxystreptamine. ► DesII is a radical SAM enzyme in involved in the biosynthesis ofd-desosamine. ► BtrN catalyzes a radical mediated dehydrogenation. ► DesII catalyzes either a radical mediated deamination or dehydrogenation. ► Here we review the current biosynthetic and mechanistic understanding of these enzymes.
Keywords: Abbreviations; amino-DOI; amino-dideoxy-; scyllo; -inosose; Cys; cysteine; 5′-dAdo; 5′-deoxyadenosine; DOI; 2-deoxy-; scyllo; -inosose; DOIA; 2-deoxy-; scyllo; -inosamine; DOS; 2-deoxystreptamine; EAL; ethanolamine ammonia-lyase; EDTA; ethylenediaminetetraacetic acid; EPR; electron paramagnetic resonance; FAD; flavin adenine dinucleotide; LAM; lysine 2,3-aminomutase; Met; methionine; NAD(P); +; oxidized nicotinamide adenine dinucleotide (phosphate); NAD(P)H; reduced nicotinamide adenine dinucleotide (phosphate); NDP; nucleotide diphosphate; PLP; pyridoxal 5′-phosphate; PMP; pyridoxamine 5′-phosphate; SAM; S; -adenosylmethionine; TyrCys; 3′-(; S; -cysteinyl)tyrosineRadical SAM enzymes; Biosynthesis; Unusual sugars; Enzyme mechanisms; DesII; BtrN
Radical SAM enzymes involved in the biosynthesis of purine-based natural products by Vahe Bandarian (pp. 1245-1253).
The radical S-adenosyl-l-methionine (SAM) superfamily is a widely distributed group of iron–sulfur containing proteins that exploit the reactivity of the high energy intermediate, 5′-deoxyadenosyl radical, which is produced by the reductive cleavage of SAM, to carry-out complex radical-mediated transformations. The reactions catalyzed by radical SAM enzymes range from simple group migrations to complex reactions in protein and RNA modification. This review will highlight three radical SAM enzymes that catalyze reactions involving modified guanosines in the biosynthesis pathways of the hypermodified tRNA base wybutosine; secondary metabolites of 7-deazapurine structure, including the hypermodified tRNA base queuosine; and the redox cofactor F420. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► Radical SAM enzymes. ► Natural product biosynthesis. ► Secondary metabolism.
Keywords: Radical SAM; Deazapurines; Wybutosine; Coenzyme F420; Biosynthesis
Radical AdoMet enzymes in complex metal cluster biosynthesis by Benjamin R. Duffus; Trinity L. Hamilton; Eric M. Shepard; Eric S. Boyd; John W. Peters; Joan B. Broderick (pp. 1254-1263).
Radical S-adenosylmethionine (AdoMet) enzymes comprise a large superfamily of proteins that engage in a diverse series of biochemical transformations through generation of the highly reactive 5′-deoxyadenosyl radical intermediate. Recent advances into the biosynthesis of unique iron–sulfur (FeS)-containing cofactors such as the H-cluster in [FeFe]-hydrogenase, the FeMo-co in nitrogenase, as well as the iron–guanylylpyridinol (FeGP) cofactor in [Fe]-hydrogenase have implicated new roles for radical AdoMet enzymes in the biosynthesis of complex inorganic cofactors. Radical AdoMet enzymes in conjunction with scaffold proteins engage in modifying ubiquitous FeS precursors into unique clusters, through novel amino acid decomposition and sulfur insertion reactions. The ability of radical AdoMet enzymes to modify common metal centers to unusual metal cofactors may provide important clues into the stepwise evolution of these and other complex bioinorganic catalysts. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► Radical AdoMet enzymes in modifying common iron–sulfur clusters are surveyed. ► Advances of radical AdoMet maturases in metal cofactor biosynthesis are reviewed. ► Biosynthetic mechanisms involving radical AdoMet enzymes are highlighted. ► Diversity of motifs that impart cluster modification functionality is discussed.
Keywords: Radical; S; -adenosylmethionine enzyme; Biosynthesis; Nitrogenase; Hydrogenase; Iron–sulfur cluster; Scaffold protein
Mechanistic studies of the radical SAM enzyme spore photoproduct lyase (SPL) by Lei Li (pp. 1264-1277).
Spore photoproduct lyase (SPL) repairs a special thymine dimer 5-thyminyl-5,6-dihydrothymine, which is commonly called spore photoproduct or SP at the bacterial early germination phase. SP is the exclusive DNA photo-damage product in bacterial endospores; its generation and swift repair by SPL are responsible for the spores' extremely high UV resistance. The early in vivo studies suggested that SPL utilizes a direct reversal strategy to repair the SP in the absence of light. The research in the past decade further established SPL as a radical SAM enzyme, which utilizes a tri-cysteine CXXXCXXC motif to harbor a [4Fe–4S] cluster. At the 1+ oxidation state, the cluster provides an electron to the S-adenosylmethionine (SAM), which binds to the cluster in a bidentate manner as the fourth and fifth ligands, to reductively cleave the CS bond associated with the sulfonium ion in SAM, generating a reactive 5′-deoxyadenosyl (5′-dA) radical. This 5′-dA radical abstracts the proR hydrogen atom from the C6 carbon of SP to initiate the repair process; the resulting SP radical subsequently fragments to generate a putative thymine methyl radical, which accepts a back-donated H atom to yield the repaired TpT. SAM is suggested to be regenerated at the end of each catalytic cycle; and only a catalytic amount of SAM is needed in the SPL reaction. The H atom source for the back donation step is suggested to be a cysteine residue (C141 in Bacillus subtilis SPL), and the H-atom transfer reaction leaves a thiyl radical behind on the protein. This thiyl radical thus must participate in the SAM regeneration process; however how the thiyl radical abstracts an H atom from the 5′-dA to regenerate SAM is unknown. This paper reviews and discusses the history and the latest progress in the mechanistic elucidation of SPL. Despite some recent breakthroughs, more questions are raised in the mechanistic understanding of this intriguing DNA repair enzyme. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.
Keywords: Radical; UV damage; Spore photoproduct lyase; DNA repair
Enzyme catalyzed radical dehydrations of hydroxy acids by Wolfgang Buckel; Jin Zhang; Peter Friedrich; Anutthaman Parthasarathy; Huan Li; Ivana Djurdjevic; Holger Dobbek; Berta M. Martins (pp. 1278-1290).
The steadily increasing field of radical biochemistry is dominated by the large family of S-adenosylmethionine dependent enzymes, the so-called radical SAM enzymes, of which several new members are discovered every year. Here we report on 2- and 4-hydroxyacyl-CoA dehydratases which apply a very different method of radical generation. In these enzymes ketyl radicals are formed by one-electron reduction or oxidation and are recycled after each turnover without further energy input. Earlier reviews on 2-hydroxyacyl-CoA dehydratases were published in 2004 [J. Kim, M. Hetzel, C.D. Boiangiu, W. Buckel, FEMS Microbiol. Rev. 28 (2004) 455–468. W. Buckel, M. Hetzel, J. Kim, Curr. Opin. Chem. Biol. 8 (2004) 462–467.]The review focuses on four types of 2-hydroxyacyl-CoA dehydratases that are involved in the fermentation of amino acids by anaerobic bacteria, especially clostridia. These enzymes require activation by one-electron transfer from an iron–sulfur protein driven by hydrolysis of ATP. The review further describes the proposed mechanism that is highlighted by the identification of the allylic ketyl radical intermediate and the elucidation of the crystal structure of 2-hydroxyisocapryloyl-CoA dehydratase. With 4-hydroxybutyryl-CoA dehydratase the crystal structure, the complete stereochemistry and the function of several conserved residues around the active site could be identified. Finally potential biotechnological applications of the radical dehydratases are presented.The action of the activator as an ‘Archerase’ shooting electrons into difficultly reducible acceptors becomes an emerging principle in anaerobic metabolism. The dehydratases may provide useful tools in biotechnology. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► 2- and 4-Hydroxyacyl-CoA contain non-acidic beta-hydrogens. ► ATP-dependent reduction generates the ketyl radical in 2-hydroxyacyl-CoA. ► Deprotonation and oxidation generates the ketyl radical of 4-hydroxybutyryl-CoA. ► 2- and 4-Hydroxyacyl-CoA dehydratases contain aconitase-like [4Fe-4S] clusters. ► 2-Hydroxyisocaproyl-CoA dehydratase comprises in addition an [4Fe-5S] cluster.
Keywords: 2-Hydroxyacyl-CoA; 4-Hydroxybutyryl-CoA; Iron–sulfur clusters; Ketyl radicals; Archerase
Radical reactions of thiamin pyrophosphate in 2-oxoacid oxidoreductases by George H. Reed; Stephen W. Ragsdale; Steven O. Mansoorabadi (pp. 1291-1298).
Thiamin pyrophosphate (TPP) is essential in carbohydrate metabolism in all forms of life. TPP-dependent decarboxylation reactions of 2-oxo-acid substrates result in enamine adducts between the thiazolium moiety of the coenzyme and decarboxylated substrate. These central enamine intermediates experience different fates from protonation in pyruvate decarboxylase to oxidation by the 2-oxoacid dehydrogenase complexes, the pyruvate oxidases, and 2-oxoacid oxidoreductases. Virtually all of the TPP-dependent enzymes, including pyruvate decarboxylase, can be assayed by 1-electron redox reactions linked to ferricyanide. Oxidation of the enamines is thought to occur via a 2-electron process in the 2-oxoacid dehydrogenase complexes, wherein acyl group transfer is associated with reduction of the disulfide of the lipoamide moiety. However, discrete 1-electron steps occur in the oxidoreductases, where one or more [4Fe–4S] clusters mediate the electron transfer reactions to external electron acceptors. These radical intermediates can be detected in the absence of the acyl-group acceptor, coenzyme A (CoASH). The π-electron system of the thiazolium ring stabilizes the radical. The extensively delocalized character of the radical is evidenced by quantitative analysis of nuclear hyperfine splitting tensors as detected by electron paramagnetic resonance (EPR) spectroscopy and by electronic structure calculations. The second electron transfer step is markedly accelerated by the presence of CoASH. While details of the second electron transfer step and its facilitation by CoASH remain elusive, expected redox properties of potential intermediates limit possible scenarios. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.► The radical intermediate in PFOR is delocalized onto the π-electron system of TPP. ► The mechanism by which coenzyme A facilitates oxidation of the radical is unknown. ► Electronic structures of radicals in PFORs from diverse species are identical.
Keywords: Radical intermediates; Thiamin pyrophosphate; Pyruvate; Coenzyme A; Acetyl-CoA; Pyruvate ferredoxin oxidoreductase; Iron–sulfur clusters; 2-Oxoacid oxidoreductase
Tryptophan tryptophylquinone biosynthesis: A radical approach to posttranslational modification by Victor L. Davidson; Aimin Liu (pp. 1299-1305).
Protein-derived cofactors are formed by irreversible covalent posttranslational modification of amino acid residues. An example is tryptophan tryptophylquinone (TTQ) found in the enzyme methylamine dehydrogenase (MADH). TTQ biosynthesis requires the cross-linking of the indole rings of two Trp residues and the insertion of two oxygen atoms onto adjacent carbons of one of the indole rings. The diheme enzyme MauG catalyzes the completion of TTQ within a precursor protein of MADH. The preMADH substrate contains a single hydroxyl group on one of the tryptophans and no crosslink. MauG catalyzes a six-electron oxidation that completes TTQ assembly and generates fully active MADH. These oxidation reactions proceed via a high valent bis-Fe(IV) state in which one heme is present as Fe(IV)=O and the other is Fe(IV) with both axial heme ligands provided by amino acid side chains. The crystal structure of MauG in complex with preMADH revealed that catalysis does not involve direct contact between the hemes of MauG and the protein substrate. Rather it is accomplished through long-range electron transfer, which presumably generates radical intermediates. Kinetic, spectrophotometric, and site-directed mutagenesis studies are beginning to elucidate how the MauG protein controls the reactivity of the hemes and mediates the long range electron/radical transfer required for catalysis. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.►MauG stabilizes a bis-Fe(IV) state with one heme as His–Fe(IV)=O and another as His–Fe(IV)–Tyr. ►MauG post-translationally modifies two tryptophan residues within a protein substrate. ►MauG mediates long range electron transfer from the protein substrate to the high valent hemes.
Keywords: Abbreviations; MADH; methylamine dehydrogenase; TTQ; tryptophan tryptophylquinone; preMADH; the biosynthetic precursor protein of MADH with incompletely synthesized TTQ; bis; -Fe(IV) MauG; redox state of MauG with one heme as Fe(IV); =; O and the other as Fe(IV); E; m; oxidation-reduction midpoint potential; Compound I; cpd I; Compound ES; cpd ESCytochrome; Electron transfer; Ferryl intermediate; Heme; MauG; Methylamine dehydrogenase