Heme and Hemoproteins

Munro, Andrew W.; Girvan, Hazel M.; McLean, Kirsty J.; Cheesman, Myles R.; Leys, D.

doi:10.1007/978-0-387-78518-9_10

Cited by 32 publications

(36 citation statements)

References 162 publications

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“…13). 122 Heme b is found in the oxygen binding hemoand myoglobins, the catalases and peroxidases, b-type cytochromes and all P 450 enzymes, 126 whilst heme c is most prevalent in their namesake, the c-type cytochromes. In addition to the effects of the porphyrin and axial ligands noted above, many other factors conspire to produce the large potential range, equivalent to a ~100 kJ.mol −1 shift in the freeenergy of reduction, and at this point they are quite well understood.…”

Section: Hemesmentioning

confidence: 99%

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

2015

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Tetrapyrrole-containing proteins are one of the most fundamental classes of enzymes in nature and it remains an open question to give a chemical rationale for the multitude of biological reactions that can be catalyzed by these pigmentprotein complexes. There are many fundamental processes where the same (i.e., chemically identical) porphyrin cofactor is involved in chemically quite distinct reactions. For example, heme is the active cofactor for oxygen transport and storage (hemoglobin, myoglobin) and for the incorporation of molecular oxygen in organic substrates (cytochrome P 450 ). It is involved in the terminal oxidation (cytochrome c oxidase) and the metabolism of H 2 O 2 (catalases and peroxidases) and catalyzes various electron transfer reactions in cytochromes. Likewise, in photosynthesis the same chlorophyll cofactor may function as a reaction center pigment (charge separation) or as an accessory pigment (exciton transfer) in light harvesting complexes (e.g., chlorophyll a). Whilst differences in the apoprotein sequences alone cannot explain the often drastic differences in physicochemical properties encountered for the same cofactor in diverse protein complexes, a critical factor for all biological functions must be the close structural interplay between bound cofactors and the respective apoprotein in addition to factors such as hydrogen bonding or electronic effects. Here, we explore how nature can use the same chemical molecule as a cofactor for chemically distinct reactions using the concept of conformational flexibility of tetrapyrroles. The multifaceted roles of tetrapyrroles are discussed in the context of the current knowledge on distorted porphyrins. Contemporary analytical methods now allow a more quantitative look at cofactors in protein complexes and the development of the field is illustrated by case studies on hemeproteins and photosynthetic complexes. Specific tetrapyrrole conformations are now used to prepare bioengineered designer proteins with specific catalytic or photochemical properties.

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Section: Hemesmentioning

confidence: 99%

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

2015

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“…This proposal, however, is based largely upon studies of animal ALA synthesis and limited studies in microbial systems. Observations in yeast (12) and some bacteria raise questions as to the universality of the model, but part of the confusion quite likely arises from the diverse nature of tetrapyrrole end products found in microorganisms (3). It is clear that additional control points exist in some bacteria that produce multiple tetrapyrrole products as part of their normal metabolism (3, 13).…”

Section: Bacterial Heme Biosynthesismentioning

confidence: 99%

“…Observations in yeast (12) and some bacteria raise questions as to the universality of the model, but part of the confusion quite likely arises from the diverse nature of tetrapyrrole end products found in microorganisms (3). It is clear that additional control points exist in some bacteria that produce multiple tetrapyrrole products as part of their normal metabolism (3, 13). Indeed, the overall molecular mechanisms for pathway regulation are not conserved even among the few bacteria examined to date and additional factors regulating bacterial ALA synthesis that were initially proposed over thirty years ago have yet to be resolved at a molecular level (13, 14).…”

Section: Bacterial Heme Biosynthesismentioning

confidence: 99%

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

Dailey¹,

Gerdes²

2015

Archives of Biochemistry and Biophysics

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Genes for chlorite dismutase-like proteins are found widely among hemesynthesizing bacteria and some Archaea. It is now known that among the Firmicutes and Actinobacteria these proteins do not possess chlorite dismutase activity but instead are essential for heme synthesis. These proteins, named HemQ, are ironcoproporphyrin (coproheme) decarboxylases that catalyze the oxidative decarboxylation of coproheme III into protoheme IX. As purified, HemQs do not contain bound heme, but readily bind exogeneously supplied heme with low micromolar affinity. The heme-bound form of HemQ has low peroxidase activity and in the presence of peroxide the bound heme may be destroyed. Thus, it is possible that HemQ may serve a dual role as a decarboxylase in heme biosynthesis and a regulatory protein in heme homeostasis.

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“…heme synthesis | Gram-positive bacteria | HemQ | coproporphyrin | HemN M any biological processes depend upon heme, an iron-containing porphyrin (1,2). This prosthetic group is essential for the function of diverse proteins, including cytochromes, globins, peroxidases, catalases, and sensors that bind diatomic gases.…”

mentioning

confidence: 99%

Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin

Dailey

Gerdes

Dailey

et al. 2015

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

153

252

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It has been generally accepted that biosynthesis of protoheme (heme) uses a common set of core metabolic intermediates that includes protoporphyrin. Herein, we show that the Actinobacteria and Firmicutes (high-GC and low-GC Gram-positive bacteria) are unable to synthesize protoporphyrin. Instead, they oxidize coproporphyrinogen to coproporphyrin, insert ferrous iron to make Fe-coproporphyrin (coproheme), and then decarboxylate coproheme to generate protoheme. This pathway is specified by three genes named hemY, hemH, and hemQ. The analysis of 982 representative prokaryotic genomes is consistent with this pathway being the most ancient heme synthesis pathway in the Eubacteria. Our results identifying a previously unknown branch of tetrapyrrole synthesis support a significant shift from current models for the evolution of bacterial heme and chlorophyll synthesis. Because some organisms that possess this coproporphyrin-dependent branch are major causes of human disease, HemQ is a novel pharmacological target of significant therapeutic relevance, particularly given high rates of antimicrobial resistance among these pathogens.

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Heme and Hemoproteins

Cited by 32 publications

References 162 publications

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

Conformational control of cofactors in nature – the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles

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

Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin

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