A widely distributed diheme enzyme from Burkholderia that displays an atypically stable bis-Fe(IV) state

Rizzolo, Kimberly; Cohen, Steven E.; Weitz, Andrew C.; Muñoz, Madeline M. López; Hendrich, Michael P.; Drennan, Catherine L.; Elliott, Sean J.

doi:10.1038/s41467-019-09020-4

Cited by 23 publications

(42 citation statements)

References 58 publications

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“…The behavior of MbnH is consistent with what has been reported for MauG (27) and suggests that MbnH is not a typical cytochrome c peroxidase, functioning to detoxify H 2 O 2 . Interestingly, upon reaction with H 2 O 2 , MbnH does develop a nIR peak at 960 nm within seconds, as observed for both Pde-MauG (23,60,64) and BthA (26) (Fig. S16).…”

Section: Mbnh Activity Assayssupporting

confidence: 59%

“…MbnH belongs to the bCcP/MauG family (PF03150). Although most members of the PF03150 family are annotated as bCcPs or MauGs, bioinformatics analysis indicates that this family is considerably more diverse than both early studies (25) and more recent analyses suggest (26). Construction of an SSN with a stringent cutoff of 1E-90 ( Fig.…”

Section: Bioinformatic Analysis Of the Bccp/maug Diheme Cytochrome C mentioning

confidence: 99%

“…MbnH forms a distinct subgroup, but analysis at different E-value cutoffs indicates it is most closely related to the MauG subfamily when compared with other protein groups within the bCcP/MauG superfamily. Several additional clusters are identifiable, including clusters associated with YhjA, the TIGR03981 enzymes, homologs of SPOA0271, and the recently discovered BthA (26) (Fig. S1).…”

Section: Characterization Of the Diheme Maug-like Protein Mbnhmentioning

confidence: 99%

“…A conserved tryptophan, Trp-113, lies between the two hemes; this residue has been proposed to mediate electron transfer in other superfamily members (48 -53) ( Fig. 3C), barring the recently-discovered BthA subfamily (26) (Fig. S1).…”

Section: Biochemical and Structural Characterization Of Mbnhmentioning

confidence: 99%

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MbnH is a diheme MauG-like protein associated with microbial copper homeostasis

Kenney¹,

Dassama²,

Manesis³

et al. 2019

Journal of Biological Chemistry

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Edited by Ruma Banerjee Methanobactins (Mbns) are ribosomally-produced, post-translationally modified peptidic copper-binding natural products produced under conditions of copper limitation. Genes encoding Mbn biosynthetic and transport proteins have been identified in a wide variety of bacteria, indicating a broader role for Mbns in bacterial metal homeostasis. Many of the genes in the Mbn operons have been assigned functions, but two genes usually present, mbnP and mbnH, encode uncharacterized proteins predicted to reside in the periplasm. MbnH belongs to the bacterial diheme cytochrome c peroxidase (bCcP)/MauG protein family, and MbnP contains no domains of known function. Here, we performed a detailed bioinformatic analysis of both proteins and have biochemically characterized MbnH from Methylosinus (Ms.) trichosporium OB3b. We note that the mbnH and mbnP genes typically co-occur and are located proximal to genes associated with microbial copper homeostasis. Our bioinformatics analysis also revealed that the bCcP/MauG family is significantly more diverse than originally appreciated, and that MbnH is most closely related to the MauG subfamily. A 2.6 Å resolution structure of Ms. trichosporium OB3b MbnH combined with spectroscopic data and peroxidase activity assays provided evidence that MbnH indeed more closely resembles MauG than bCcPs, although its redox properties are significantly different from those of MauG. The overall similarity of MbnH to MauG suggests that MbnH could post-translationally modify a macromolecule, such as internalized CuMbn or its uncharacterized partner protein, MbnP. Our results indicate that MbnH is a MauG-like diheme protein that is likely involved in microbial copper homeostasis and represents a new family within the bCcP/MauG superfamily. Natural products that sequester and import vital and toxic metal ions play important roles in maintaining metal homeostasis in many species. Most well-studied are bacterial small molecules that bind ferric iron and are known as siderophores (iron "carriers") (1). In recent years, similar molecules that bind other metals have been discovered and characterized (2). One of these is a family of copper-binding compounds called methanobactins (Mbn) 5 (3, 4), which are produced from ribosomally synthesized peptides. All Mbns contain post-translational modifications that include nitrogen-containing heterocycles (oxazolones and pyrazinedione/diols) and neighboring thioamide/enethiol groups, and many have other less widespread modifications including "N-terminal" carbonyl groups (5, 6), intramolecular disulfide bonds (3, 6), and sulfonated threonines (7, 8). Of these functional groups, the N-heterocycles and thioamides provide ligands that chelate a copper ion. Mbns bind both Cu I and Cu II with high affinity (binding constants of 10 19-21 M Ϫ1 for Cu I and 10 11-14 M Ϫ1 for Cu II) (7-9); upon binding, the latter is quickly reduced to Cu I via an unknown mechanism. Under copper-limited conditions, some methanotrophs, bacteria that metabolize methane under...

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Section: Mbnh Activity Assayssupporting

confidence: 59%

Section: Bioinformatic Analysis Of the Bccp/maug Diheme Cytochrome C mentioning

confidence: 99%

Section: Characterization Of the Diheme Maug-like Protein Mbnhmentioning

confidence: 99%

Section: Biochemical and Structural Characterization Of Mbnhmentioning

confidence: 99%

See 2 more Smart Citations

MbnH is a diheme MauG-like protein associated with microbial copper homeostasis

Kenney¹,

Dassama²,

Manesis³

et al. 2019

Journal of Biological Chemistry

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“…An SSN was built with the diamond output using 80% identity and 80% coverage threshold. This coverage threshold is commonly used in SSN studies 33,35,72 and we also tested 4 other similarity thresholds: 70%, 75%, 85%, and 90%. We selected the intermediary 80% identity threshold to minimize the amount of singletons while maximizing the functional homogeneity between linked proteins.…”

Section: Methodsmentioning

confidence: 99%

Towards omics-based predictions of planktonic functional composition from environmental data

2021

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Marine microbes play a crucial role in climate regulation, biogeochemical cycles, and trophic networks. Unprecedented amounts of data on planktonic communities were recently collected, sparking a need for innovative data-driven methodologies to quantify and predict their ecosystemic functions. We reanalyze 885 marine metagenome-assembled genomes through a network-based approach and detect 233,756 protein functional clusters, from which 15% are functionally unannotated. We investigate all clusters’ distributions across the global ocean through machine learning, identifying biogeographical provinces as the best predictors of protein functional clusters’ abundance. The abundances of 14,585 clusters are predictable from the environmental context, including 1347 functionally unannotated clusters. We analyze the biogeography of these 14,585 clusters, identifying the Mediterranean Sea as an outlier in terms of protein functional clusters composition. Applicable to any set of sequences, our approach constitutes a step towards quantitative predictions of functional composition from the environmental context.

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An S=1 Iron(IV) Intermediate Revealed in a Non‐Heme Iron Enzyme‐Catalyzed Oxidative C−S Bond Formation

Paris,

Hu,

Wen

et al. 2023

Angewandte Chemie

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Ergothioneine (ESH) and ovothiol A (OSHA) are two natural thiol‐histidine derivatives. ESH has been implicated as a longevity vitamin and OSHA inhibits the proliferation of hepatocarcinoma. The key biosynthetic step of ESH and OSHA in the aerobic pathways is the O2‐dependent C−S bond formation catalyzed by non‐heme iron enzymes (e.g., OvoA in ovothiol biosynthesis), but due to the lack of identification of key reactive intermediate the mechanism of this novel reaction is unresolved. In this study, we report the identification and characterization of a kinetically competent S=1 iron(IV) intermediate supported by a four‐histidine ligand environment (three from the protein residues and one from the substrate) in enabling C−S bond formation in OvoA from Methyloversatilis thermotoleran, which represents the first experimentally observed intermediate spin iron(IV) species in non‐heme iron enzymes. Results reported in this study thus set the stage to further dissect the mechanism of enzymatic oxidative C−S bond formation in the OSHA biosynthesis pathway. They also afford new opportunities to study the structure‐function relationship of high‐valent iron intermediates supported by a histidine rich ligand environment.

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A widely distributed diheme enzyme from Burkholderia that displays an atypically stable bis-Fe(IV) state

Cited by 23 publications

References 58 publications

MbnH is a diheme MauG-like protein associated with microbial copper homeostasis

MbnH is a diheme MauG-like protein associated with microbial copper homeostasis

Towards omics-based predictions of planktonic functional composition from environmental data

An S=1 Iron(IV) Intermediate Revealed in a Non‐Heme Iron Enzyme‐Catalyzed Oxidative C−S Bond Formation

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