MauG, a diheme enzyme that catalyzes tryptophan tryptophylquinone biosynthesis by remote catalysis

Abstract

MauG contains two c-type hemes with atypical physical and catalytic properties. While most c-type cytochromes function simply as electron transfer mediators, MauG catalyzes the completion of tryptophan tryptophylquinone (TTQ) biosynthesis within a precursor protein of methylamine dehydrogenase. This posttranslational modification is a six-electron oxidation that requires crosslinking of two Trp residues, oxygenation of a Trp residue and oxidation of the resulting quinol to TTQ. These reactions proceed via a bis-FeIV state in which one heme is present as FeIV=O and the other is FeIV with axial heme ligands provided by His and Tyr side chains. Catalysis does not involve direct contact between the protein substrate and either heme of MauG. Instead it is accomplished by remote catalysis using a hole hopping mechanism of electron transfer in which Trp residues of MauG are reversibly oxidized. In this process, long range electron transfer is coupled to the radical mediated chemical reactions that are required for TTQ biosynthesis.

Anammox Biochemistry: a Tale of Heme c Proteins

“…(C) structuring provides a solid platform for protein-protein interactions as well as for the binding of cofactors that direct activity in diverse enzymes such as NirS nitrite reductase, NO reductases, and methanol and methylamine dehydrogenases [69,70]. The structure of the g subunit highly resembles those of CCPs [71,72] and the MauG protein involved in the synthesis of tryptophan tryptophylquinone cofactor of methylamine dehydrogenase [73,74]. As it is the case for CCPs and MauG, the HZS g subunit contains two c-type hemes.…”

Combining metagenomics with metaproteomics and stable isotope probing reveals metabolic pathways used by a naturally occurring marine methylotroph

“…One gene cluster, mauFBEDAGLMN , contains genes encoding the large ( mauB ) and small ( mauA ) subunit of methylamine dehydrogenase, a tryptophan tryptophylquinone‐dependent dehydrogenase of the same protein family as the PQQ‐dependent dehydrogenases, as well as further accessory genes required for the activity of this enzyme (http://onlinelibrary.wiley.com/doi/10.1111/1462-2920.12935/suppinfo; Anthony, ; McIntire et al ., ; Davidson, ; Shin and Davidson, ). Methylamine dehydrogenase catalyses the direct oxidation of methylamine to formaldehyde and ammonium and is typically found in Proteobacteria that use methylamine as a carbon source (Chistoserdova, ; Shin and Davidson, ; Wischer et al ., ). The second gene cluster encodes genes for gamma‐glutamylmethylamide (GMA) synthetase ( gmaS ), N ‐methylglutamate (NMG) synthase ( mgsABC ) and NMG dehydrogenase ( mgdABCD ).…”

Functional and structural characterization of a flavoprotein monooxygenase essential for biogenesis of tryptophylquinone cofactor

“…The role played by QhpG in the quinone cofactor biogenesis is worth comparing with those of the modifying enzymes involved in other tryptophylquinone-generating systems 6 , such as MauG 4 , 36 , 37 , a di-heme protein participating in the biosynthesis of tryptophan tryptophylquinone (TTQ), the first tryptophylquinone cofactor discovered in methylamine dehydrogenase (MADH) 38 , and LodB 39 and GoxB 40 – 42 , flavoproteins required for the formation of CTQ identified in l-lysine ε-oxidase (LodA) 43 and glycine oxidase (GoxA) 44 , respectively. Most importantly, the target Trp residue in the substrate proteins for MauG, LodB, and GoxB is a mono-(7-)hydroxy-Trp 4 , 36 , 37 , whereas that for QhpG is an unmodified Trp. Thus, QhpG inserts both oxygen atoms into the Trp of CTQ, whereas in the biogenesis of TTQ in MADH and CTQ in LodA and GoxA, the substrate for the modifying enzyme has the first hydroxyl present and only the second is added along with the formation of the Trp–Trp or Trp–Cys crosslink.…”