Utilization of host iron sources by Corynebacterium diphtheriae: identification of a gene whose product is homologous to eukaryotic heme oxygenases and is required for acquisition of iron from heme and hemoglobin

Schmitt, Michael

doi:10.1128/jb.179.3.838-845.1997

Cited by 217 publications

(258 citation statements)

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“…In higher plants, algae, and cyanobacteria, HO generates the open tetrapyrroles as lightharvesting pigments (8). HO has also been identified in several pathogenic bacteria, where its role appears to be the essential "mining" of iron from hemes in the host (9,10). Plant and bacterial HOs are soluble and somewhat shorter (ϳ200 residues) (9, 10) than mammalian HO (11).…”

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confidence: 99%

“…We report herein on the extension of our 1 H NMR investigation to HmuO, the 216-residue soluble bacterial HO from C. diphtheriae (10), using hHO as a homology model (21). Functional (26,27) and spectroscopic (27,28) studies, as well as mutagenesis (29,30), have confirmed the same mechanism and stereospecificity as for mammalian HOs, although the turnover rate is slower (27); the enzyme has been crystallized (31), and the structure of the substrate hemin complex has been refined to 1.4-Å resolution.…”

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confidence: 99%

“…Plant and bacterial HOs are soluble and somewhat shorter (ϳ200 residues) (9, 10) than mammalian HO (11). Among the characterized bacterial HOs, sequence homology to the more extensively studied mammalian HO varies from relative high (33% sequence identity/70% similarity) for HmuO from Corynebacterium diphtheriae (10) to low (Ͻ25%) for HemO from Neisseria meningitides (9).…”

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Solution 1H NMR Investigation of the Active Site Molecular and Electronic Structures of Substrate-bound, Cyanide-inhibited HmuO, a Bacterial Heme Oxygenase fromCorynebacterium diphtheriae

Syvitski

Chu

et al. 2003

Journal of Biological Chemistry

117

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Solution 1H NMR Investigation of the Active Site Molecular and Electronic Structures of Substrate-bound, Cyanide-inhibited HmuO, a Bacterial Heme Oxygenase fromCorynebacterium diphtheriae

Syvitski

Chu

et al. 2003

Journal of Biological Chemistry

117

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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).…”

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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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“…Siderophores are secreted molecules that bind free iron and then are captured by bacterial surface receptors that deliver iron for transport across the cytoplasmic membrane (4). In addition to retrieving free iron, bacteria also can acquire iron that is bound by various proteins (4,5). Iron acquisition is critical for the establishment of human infections, because several host proteins sequester iron and reduce the concentration of free iron within tissues in an effort to prevent bacterial growth.…”

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An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis

Mazmanian

Ton‐That

et al. 2002

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

343

355

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Sortase (SrtA), an enzyme that anchors surface proteins to the cell wall of Gram-positive bacteria, cleaves sorting signals at the LPXTG motif. We have identified a second sortase (SrtB) in the Gram-positive pathogen Staphylococcus aureus that is required for anchoring of a surface protein with a NPQTN motif. Purified SrtB cleaves NPQTN-bearing peptides in vitro, and a srtB mutant is defective in the persistence of animal infections. srtB is part of an iron-regulated locus called iron-responsive surface determinants (isd), which also contains a ferrichrome transporter and surface proteins with NPQTN and LPXTG motifs. Cell wall-anchored surface proteins and the isd locus seem involved in a novel mechanism of iron acquisition that is important for bacterial pathogenesis.

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Utilization of host iron sources by Corynebacterium diphtheriae: identification of a gene whose product is homologous to eukaryotic heme oxygenases and is required for acquisition of iron from heme and hemoglobin

Cited by 217 publications

References 55 publications

Solution 1H NMR Investigation of the Active Site Molecular and Electronic Structures of Substrate-bound, Cyanide-inhibited HmuO, a Bacterial Heme Oxygenase fromCorynebacterium diphtheriae

Solution 1H NMR Investigation of the Active Site Molecular and Electronic Structures of Substrate-bound, Cyanide-inhibited HmuO, a Bacterial Heme Oxygenase fromCorynebacterium diphtheriae

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

An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis

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