Heme Oxygenase Structure and Mechanism

Montellanoa, Paul R. Ortiz De; Auclairb, Karine

doi:10.1016/b978-0-08-092386-4.50013-7

Cited by 61 publications

(79 citation statements)

References 187 publications

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“…58−60 Although the absorption spectrum of the HO-1 Fe II –O 2 complex is similar to that of oxymyoglobin, 61 the Raman spectrum shows a unique oxygen-isotope shift suggesting that the bound O 2 is highly bent. 62 The structure of the bacterial Fe II –O 2 heme–HmuO complex confirmed that the 110° Fe–O–O bond angle is due to interaction of the O 2 ligand with the distal helix (Figure 3B).…”

Section: Oxygen Activation and Heme Hydroxylation: The Initial Step Imentioning

confidence: 97%

Heme Utilization by Pathogenic Bacteria: Not All Pathways Lead to Biliverdin

Wilks

Ikeda‐Saito

2014

Acc. Chem. Res.

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ConspectusThe eukaryotic heme oxygenases (HOs) (E.C. 1.14.99.3) convert heme to biliverdin, iron, and carbon monoxide (CO) in three successive oxygenation steps. Pathogenic bacteria require iron for survival and infection. Extracellular heme uptake from the host plays a critical role in iron acquisition and virulence. In the past decade, several HOs required for the release of iron from extracellular heme have been identified in pathogenic bacteria, including Corynebacterium diphtheriae, Neisseriae meningitides, and Pseudomonas aeruginosa. The bacterial enzymes were shown to be structurally and mechanistically similar to those of the canonical eukaryotic HO enzymes. However, the recent discovery of the structurally and mechanistically distinct noncanonical heme oxygenases of Staphylococcus aureus and Mycobacterium tuberculosis has expanded the reaction manifold of heme degradation. The distinct ferredoxin-like structural fold and extreme heme ruffling are proposed to give rise to the alternate heme degradation products in the S. aureus and M. tuberculosis enzymes. In addition, several “heme-degrading factors” with no structural homology to either class of HOs have recently been reported. The identification of these “heme-degrading proteins” has largely been determined on the basis of in vitro heme degradation assays. Many of these proteins were reported to produce biliverdin, although no extensive characterization of the products was performed. Prior to the characterization of the canonical HO enzymes, the nonenzymatic degradation of heme and heme proteins in the presence of a reductant such as ascorbate or hydrazine, a reaction termed “coupled oxidation”, served as a model for biological heme degradation. However, it was recognized that there were important mechanistic differences between the so-called coupled oxidation of heme proteins and enzymatic heme oxygenation. In the coupled oxidation reaction, the final product, verdoheme, can readily be converted to biliverdin under hydrolytic conditions. The differences between heme oxygenation by the canonical and noncanonical HOs and coupled oxidation will be discussed in the context of the stabilization of the reactive FeIII–OOH intermediate and regioselective heme hydroxylation. Thus, in the determination of heme oxygenase activity in vitro, it is important to ensure that the reaction proceeds through successive oxygenation steps. We further suggest that when bacterial heme degradation is being characterized, a systems biology approach combining genetics, mechanistic enzymology, and metabolite profiling should be undertaken.

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Section: Oxygen Activation and Heme Hydroxylation: The Initial Step Imentioning

confidence: 97%

Heme Utilization by Pathogenic Bacteria: Not All Pathways Lead to Biliverdin

Wilks

Ikeda‐Saito

2014

Acc. Chem. Res.

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“…Until relatively recently, the only enzymes known to catalyze the removal of iron from heme were members of the heme oxygenase (HO) family (Pfam identifier PF01126). 89 However, it became apparent in the early 2000s that many important pathogens that survive on heme did not possess an HO. This led to the discovery of the IsdG-family of proteins which, in Staphylococcus aureus , have been shown to act at the terminus of a cascade of proteins that strip heme from hemoglobin and shuttle it through the cell wall.…”

Section: Heme As a Substrate And Productmentioning

confidence: 99%

“…Notably, the well-described HOs have a network of water molecules in the distal pocket, which supply key hydrogen bonds and a conduit by which protons can move in and out of the active site. 89 How IsdGs stabilize Fe/O 2 intermediates without such a network, and how they convey molecules in/out of the pocket is not clear. Finally, many species possess not just one but two paralogous proteins from the IsdG family, differing from each other only subtly in sequence in structure.…”

Section: Heme As a Substrate And Productmentioning

confidence: 99%

Substrate, product, and cofactor: The extraordinarily flexible relationship between the CDE superfamily and heme

Celis¹,

DuBois²

2015

Archives of Biochemistry and Biophysics

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PFam Clan 0032, also known as the CDE superfamily, is a diverse group of at least 20 protein families sharing a common α, β-barrel domain. Of these, six different groups bind heme inside the barrel’s interior, using it alternately as a cofactor, substrate, or product. Focusing on these six, an integrated picture of structure, sequence, taxonomy, and mechanism is presented here, detailing how a single structural motif might be able to mediate such an array of functions with one of nature’s most important small molecules.

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“…Biliverdin is further metabolized to bilirubin and excreted in the bile, conjugated with glucuronic acid [75]. Similar catalytic mechanisms by HO-like proteins are postulated to also occur in bacteria and plants [76].…”

Section: Introductionmentioning

confidence: 99%

Heme and blood-feeding parasites: friends or foes?

et al. 2010

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Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with diverse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification.

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Heme Oxygenase Structure and Mechanism

Cited by 61 publications

References 187 publications

Heme Utilization by Pathogenic Bacteria: Not All Pathways Lead to Biliverdin

Heme Utilization by Pathogenic Bacteria: Not All Pathways Lead to Biliverdin

Substrate, product, and cofactor: The extraordinarily flexible relationship between the CDE superfamily and heme

Heme and blood-feeding parasites: friends or foes?

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