HemQ: An iron-coproporphyrin oxidative decarboxylase for protoheme synthesis in Firmicutes and Actinobacteria

Dailey, Harry A.; Gerdes, Svetlana

doi:10.1016/j.abb.2015.02.017

Cited by 40 publications

(50 citation statements)

References 61 publications

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“…Recently, Dailey and co-workers proposed a novel haeme biosynthesis pathway for Gram-positive bacteria in which HemQ acts as a coprohaeme decarboxylase to yield protohaeme; in this reaction, coprohaeme has to bind to HemQ, react with presumably H 2 O 2 to release two CO 2 molecules to yield and release haeme b. This finding is also supported by other studies [7][8][9][10]. Nevertheless, the mechanism of this reaction is unknown.…”

Section: Introductionsupporting

confidence: 76%

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From chlorite dismutase towards HemQ–the role of the proximal H-bonding network in haeme binding

et al. 2016

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SynopsisChlorite dismutase (Cld) and HemQ are structurally and phylogenetically closely related haeme enzymes differing fundamentally in their enzymatic properties. Clds are able to convert chlorite into chloride and dioxygen, whereas HemQ is proposed to be involved in the haeme b synthesis of Gram-positive bacteria. A striking difference between these protein families concerns the proximal haeme cavity architecture. The pronounced H-bonding network in Cld, which includes the proximal ligand histidine and fully conserved glutamate and lysine residues, is missing in HemQ. In order to understand the functional consequences of this clearly evident difference, specific hydrogen bonds in Cld from 'Candidatus Nitrospira defluvii' (NdCld) were disrupted by mutagenesis. The resulting variants (E210A and K141E) were analysed by a broad set of spectroscopic (UV-vis, EPR and resonance Raman), calorimetric and kinetic methods. It is demonstrated that the haeme cavity architecture in these protein families is very susceptible to modification at the proximal site. The observed consequences of such structural variations include a significant decrease in thermal stability and also affinity between haeme b and the protein, a partial collapse of the distal cavity accompanied by an increased percentage of low-spin state for the E210A variant, lowered enzymatic activity concomitant with higher susceptibility to self-inactivation. The high-spin (HS) ligand fluoride is shown to exhibit a stabilizing effect and partially restore wild-type Cld structure and function. The data are discussed with respect to known structure-function relationships of Clds and the proposed function of HemQ as a coprohaeme decarboxylase in the last step of haeme biosynthesis in Firmicutes and Actinobacteria.

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Section: Introductionsupporting

confidence: 76%

“…These frequencies do not vary in the pH range 5.5-9. 8. The observed ν(Fe-C)/ν(CO) frequencies are typical of haeme-CO adducts that have little interaction with the distal protein matrix.…”

Section: Co Binding To Wild-type Ndcld and The Variants E210a And K141ementioning

confidence: 92%

From chlorite dismutase towards HemQ–the role of the proximal H-bonding network in haeme binding

et al. 2016

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“…The existence of an anaerobic mechanism for heme degradation is consistent with (i) the recent revelations in the heme biosynthetic pathways (20,37), (ii) the characterization of radical SAM enzymes involved in catalyzing important steps in the anaerobic biosynthesis of protoheme (19,25), and (iii) recent observations that heme degradation has evolved to suit the physiological needs of the organism (12). Our in vitro data suggest that ChuW functions as a RSMT that methylates heme as part of a decyclization mechanism, resulting in an open tetrapyrrole and the release of the essential nutrient iron (Fig.…”

Section: Discussionsupporting

confidence: 53%

Radical new paradigm for heme degradation in Escherichia coli O157:H7

LaMattina

Nix

Lanzilotta

2016

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

107

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All of the heme-degrading enzymes that have been characterized to date require molecular oxygen as a cosubstrate. Escherichia coli O157:H7 has been shown to express heme uptake and transport proteins, as well as use heme as an iron source. This enteric pathogen colonizes the anaerobic space of the lower intestine in mammals, yet no mechanism for anaerobic heme degradation has been reported. Herein we provide evidence for an oxygen-independent heme-degradation pathway. Specifically, we demonstrate that ChuW is a radical S-adenosylmethionine methyltransferase that catalyzes a radical-mediated mechanism facilitating iron liberation and the production of the tetrapyrrole product we termed “anaerobilin.” We further demonstrate that anaerobilin can be used as a substrate by ChuY, an enzyme that is coexpressed with ChuW in vivo along with the heme uptake machinery. Our findings are discussed in terms of the competitive advantage this system provides for enteric bacteria, particularly those that inhabit an anaerobic niche in the intestines.

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“…This has frequently been referred to as the classic pathway, and until recently, it was believed to be universal in protoheme-synthesizing bacteria. This generic model was demonstrated to be incorrect with the discovery that Gram-positive bacteria utilize an alternate route, which can be viewed as an evolutionary transition between the siroheme-dependent pathway found first in archaea and described above and the classical pathway found in Gram-negative bacteria and eukaryotes (35,43,44). We refer to this pathway as the coproporphyrinProkaryotic Heme Biosynthesis Microbiology and Molecular Biology Reviews dependent (CPD) branch since it uniquely contains coproporphyrin III as an intermediate (Fig.…”

Section: The Coproporphyrin-dependent Branchmentioning

confidence: 99%

“…It is now known that some archaea and sulfate-reducing bacteria synthesize siroheme and then convert it to protoheme (11,42), Gram-positive hemesynthesizing bacteria go through a set of enzymes that utilize a coproporphyrin intermediate (35,(43)(44)(45), and Gram-negative bacteria have a set of enzymes that go through a protoporphyrin intermediate (35). These various pathways to heme in prokaryotes have acquired a variety of common names, such as primitive (46), alternate (11), transitional (43), and classic.…”

Section: Introduction Wmentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

Self Cite

272

335

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SUMMARY The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzyme-step process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gram-negative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized.

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HemQ: An iron-coproporphyrin oxidative decarboxylase for protoheme synthesis in Firmicutes and Actinobacteria

Cited by 40 publications

References 61 publications

From chlorite dismutase towards HemQ–the role of the proximal H-bonding network in haeme binding

From chlorite dismutase towards HemQ–the role of the proximal H-bonding network in haeme binding

Radical new paradigm for heme degradation in Escherichia coli O157:H7

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

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