<i>Bacillus anthracis</i>IsdG, a Heme-Degrading Monooxygenase

Skaar, Eric P.; Gaspar, Andrew H.; Schneewind, Olaf

doi:10.1128/jb.188.3.1071-1080.2006

Cited by 106 publications

(139 citation statements)

References 57 publications

(96 reference statements)

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“…Consistent with earlier studies of haem monooxygenases (Kunkle & Schmitt, 2007;Puri & O'Brian, 2006;Skaar et al, , 2006, we observed apparent degradation of the bound haem substrate as (Puri & O'Brian, 2006;Skaar et al, , 2006. This suggests that an additional factor may be needed in vivo to dissociate the degradation product from the protein.…”

Section: A Gaballa and J D Helmannsupporting

confidence: 80%

“…Importantly, members of the HmoA subfamily are found in the human pathogens B. anthracis and Bacillus cereus, where they may play a role in iron acquisition during infection. The overall sequence conservation with B. anthracis and S. aureus IsdG (Skaar et al, 2006), and the retention of most of the known active site residues, suggests a mode of activity similar to IsdG (Reniere et al, 2010). Indeed, both HmoA and HmoB bind haemin with approximately 1 : 1 stoichiometry, and the characteristic haemin absorbance decreases upon addition of reductant.…”

Section: Discussionmentioning

confidence: 99%

“…Haemin degradation was assayed using ascorbate as reductant in 50 mM Tris/HCl (pH 8) and 150 mM NaCl buffer. Ascorbic acid-dependent degradation of haem bound to HmoA or HmoB was monitored in the presence and absence of catalase, as described by Skaar et al (2006). Site-directed mutagenesis of hmoA and hmoB was done using PCR and overlap extension (Ho et al, 1989).…”

Section: Methodsmentioning

confidence: 99%

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Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases

Gaballa

Helmann

2011

Microbiology

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Identification of genes regulated by the ferric uptake regulator (Fur) protein has provided insights into the diverse mechanisms of adaptation to iron limitation. In the soil bacterium Bacillus subtilis, Fur senses iron sufficiency and represses genes that enable iron uptake, including biosynthetic and transport genes for the siderophore bacillibactin and uptake systems for siderophores produced by other organisms. We here demonstrate that Fur regulates hmoA (formerly yetG), which encodes a haem monooxygenase. HmoA is the first characterized member of a divergent group of putative monooxygenases that cluster separately from the well-characterized IsdG family. B. subtilis also encodes an IsdG family protein designated HmoB (formerly YhgC). Unlike hmoA, hmoB is constitutively expressed and not under Fur control. HmoA and HmoB both bind haemin in vitro with approximately 1 : 1 stoichiometry and degrade haemin in the presence of an electron donor. Mutational and spectroscopic analyses indicate that HmoA and HmoB have distinct active site architectures and interact differently with haem. We further show that B. subtilis can use haem as an iron source, but that this ability is independent of HmoA and HmoB.

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Section: A Gaballa and J D Helmannsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases

Gaballa

Helmann

2011

Microbiology

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“…This class of enzymes degrades heme into biliverdin, CO, and iron (6). Furthermore, non-HO homolog heme degrading enzymes have been reported for some bacteria (7)(8)(9). Although heme degradation by this class of weakly similar enzymes has been confirmed by CO production, the precise nature of the resulting products remains controversial (10).…”

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confidence: 99%

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact

Létoffé

Heuck

Delepelaire

et al. 2009

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

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126

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Because heme is a major iron-containing molecule in vertebrates, the ability to use heme-bound iron is a determining factor in successful infection by bacterial pathogens. Until today, all known enzymes performing iron extraction from heme did so through the rupture of the tetrapyrrol skeleton. Here, we identified 2 Escherichia coli paralogs, YfeX and EfeB, without any previously known physiological functions. YfeX and EfeB promote iron extraction from heme preserving the tetrapyrrol ring intact. This novel enzymatic reaction corresponds to the deferrochelation of the heme. YfeX and EfeB are the sole proteins able to provide iron from exogenous heme sources to E. coli. YfeX is located in the cytoplasm. EfeB is periplasmic and enables iron extraction from heme in the periplasm and iron uptake in the absence of any heme permease. YfeX and EfeB are widespread and highly conserved in bacteria. We propose that their physiological function is to retrieve iron from heme

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“…HO has been identified in a wide array of organisms, including mammals (1, 2), insects (3,4), and photosynthetic organisms (5,6). Of particular interest, HO is present in many pathogenic bacteria (7)(8)(9)(10), including Neisseria meningitidis (11) and Pseudomonas aeruginosa (12). These pathogenic bacteria have developed sophisticated heme uptake systems that harness the iron from hemecontaining proteins present in the host (13)(14)(15).…”

mentioning

confidence: 99%

Diatomic Ligand Discrimination by the Heme Oxygenases from Neisseria meningitidis and Pseudomonas aeruginosa

Friedman

Meharenna

Wilks

et al. 2007

Journal of Biological Chemistry

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Heme oxygenases have an increased binding affinity for O 2 relative to CO. Such discrimination is critical to the function of HO enzymes because one of the main products of heme catabolism is CO. Kinetic studies of mammalian and bacterial HO proteins reveal a significant decrease in the dissociation rate of O 2 relative to other heme proteins such as myoglobin. Here we report the kinetic rate constants for the binding of O 2 and CO by the heme oxygenases from Neisseria meningitidis (nmHO) and Pseudomonas aeruginosa (paHO). A combination of stoppedflow kinetic and laser flash photolysis experiments reveal that nmHO and paHO both maintain a similar degree of ligand discrimination as mammalian HO-1 and the HO from Corynebacterium diphtheriae. However, in addition to the observed decrease in dissociation rate for O 2 by both nmHO and paHO, kinetic analyses show an increase in dissociation rate for CO by these two enzymes. The crystal structures of nmHO and paHO both contain significant differences from the mammalian HO-1 and bacterial C. diphtheriae HO structures, which suggests a structural basis for ligand discrimination in nmHO and paHO. Heme oxygenase (HO)2 catalyzes the oxidative degradation of heme to biliverdin, iron, and CO (Fig. 1). HO has been identified in a wide array of organisms, including mammals (1, 2), insects (3, 4), and photosynthetic organisms (5, 6). Of particular interest, HO is present in many pathogenic bacteria (7-10), including Neisseria meningitidis (11) and Pseudomonas aeruginosa (12). These pathogenic bacteria have developed sophisticated heme uptake systems that harness the iron from hemecontaining proteins present in the host (13-15). The HO enzymes from N. meningitidis (nmHO) and P. aeruginosa (paHO) are both essential for the utilization of iron from imported heme, and the crystal structures of these two bacterial HO enzymes have now been solved (16,17). Although most HOs hydroxylate exclusively the ␣-meso heme carbon (Fig. 1), paHO is unusual because the ␥-meso carbon is the predominate site of hydroxylation (18) even though the structure paHO is very much the same as other HOs. The difference in hydroxylation patterns is due to an ϳ100 o rotation of the heme in paHO relative to other HOs which places the ␥-meso carbon at the same position in the active site as the ␣-meso carbon in other HOs (16).The Fe(II) atom of the heme prosthetic group of heme proteins is an efficient binder of O 2 , NO, and CO, and the binding by heme proteins of these diatomic molecules is of critical importance to physiological processes such as respiration, vasodilation, and neurotransmission (19 -21). A common feature shared by all heme proteins is the need to not only bind its target ligand but also to discriminate against the binding of heme ligands of similar size and shape. Fe(II) adducts of CO are normally linear because backbonding is optimized by the overlap of Fe(II) d-orbitals with the empty * orbitals of . In contrast, Fe(II)-NO and Fe(II)-O 2 are naturally bent in order to maximize overlap with ...

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Bacillus anthracisIsdG, a Heme-Degrading Monooxygenase

Cited by 106 publications

References 57 publications

Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases

Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact

Diatomic Ligand Discrimination by the Heme Oxygenases from Neisseria meningitidis and Pseudomonas aeruginosa

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