Structural biology of heme binding in the Staphylococcus aureus Isd system

Grigg, J.C.; Ukpabi, Georgia; Gaudin, C.F.M.; Murphy, M.E.P.

doi:10.1016/j.jinorgbio.2009.09.012

Cited by 129 publications

(151 citation statements)

References 84 publications

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“…Recently, Hannauer et al (2015) reported the involvement of two additional reductases, NrtA and IruO, in haem iron removal by Staphylococcus aureus. The Isd-mediated haem uptake system of Staphylococcus aureus was comprehensively reviewed by Hammer & Skaar (2011) and its significance in Staphylococcus aureus infections is demonstrated by its requirement for full virulence in several models of pathogenesis, as reviewed by Grigg et al (2010).…”

Section: Haem Uptake Systemsmentioning

confidence: 99%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

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Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.

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Section: Haem Uptake Systemsmentioning

confidence: 99%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

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“…The active sites of the Isd enzymes and classic HOs also differ significantly in that heme bound at the active sites of the Isd enzymes is highly ruffled (4,5,19). Normal-coordinate structural decomposition (NSD) analysis (20) reveals that the heme at the active sites of these enzymes is distorted 2.1 Å out of plane, far more than has been observed for any other heme-binding protein.…”

mentioning

confidence: 96%

“…direct electrochemistry | NMR spectroscopy | X-ray crystallography I sdG and IsdI are paralogues that catalyze protoheme IX degradation as components of the iron-regulated surface determinant (Isd) system of Staphylococcus aureus (1)(2)(3)(4). Recently, the heme oxidation products formed by these enzymes have been shown to be a nearly equal mixture of 5-oxo-δ-bilirubin and 15-oxo-β-bilirubin (staphylobilins) (5).…”

mentioning

confidence: 99%

“…Normal-coordinate structural decomposition (NSD) analysis (20) reveals that the heme at the active sites of these enzymes is distorted 2.1 Å out of plane, far more than has been observed for any other heme-binding protein. This distinctive structural characteristic has been suggested to be a major factor in the mechanism by which these enzymes oxidize heme (4,5,19).…”

mentioning

confidence: 99%

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Electronic properties of the highly ruffled heme bound to the heme degrading enzyme IsdI

Takayama

Ukpabi

Murphy

et al. 2011

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

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159

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IsdI, a heme-degrading protein from Staphylococcus aureus , binds heme in a manner that distorts the normally planar heme prosthetic group to an extent greater than that observed so far for any other heme-binding protein. To understand better the relationship between this distinct structural characteristic and the functional properties of IsdI, spectroscopic, electrochemical, and crystallographic results are reported that provide evidence that this heme ruffling is essential to the catalytic activity of the protein and eliminates the need for the water cluster in the distal heme pocket that is essential for the activity of classical heme oxygenases. The lack of heme orientational disorder in 1 H-NMR spectra of the protein argues that the catalytic formation of β- and δ-biliverdin in nearly equal yield results from the ability of the protein to attack opposite sides of the heme ring rather than from binding of the heme substrate in two alternative orientations.

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“…Iron uptake in Gram-positive bacteria has been well described (Braun & Hantke, 2011;Grigg et al, 2010). In Staphylococcus aureus a family of Isd (iron-regulated surface determinants) proteins is facilitating haem uptake across the cell wall.…”

Section: Discussionmentioning

confidence: 99%

Iron restriction-induced adaptations in the wall proteome of Candida albicans

et al. 2013

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The opportunistic fungal pathogen Candida albicans has developed various ways to overcome iron restriction in a mammalian host. Using different surface proteins, among them membrane-and wall-localized glycosylphosphatidylinositol (GPI) proteins, it can exploit iron from host haemoglobin, ferritin and transferrin. Culturing C. albicans in rich medium supplemented with the ferrous iron chelator bathophenanthroline disulfonic acid or in the minimal medium yeast nitrogen base resulted in a strong decrease of the iron content of the cells. MS analysis of the changes in the wall proteome of C. albicans upon iron restriction showed a strong increase in the levels of the GPI-modified adhesin Als3, which also serves as a ferritin receptor, and of the GPI-modified CFEM (common in fungal extracellular membranes) domain-containing proteins Csa1, Pga7, Pga10, and Rbt5. The wall levels of the GPI-modified proteins Hyr1, the adhesin Als4 and the copper-and zinc-containing superoxide dismutase Sod4 also strongly increased, whereas the levels of Tos1 (a non-GPI protein) and the GPI-modified adhesin Als2 strongly decreased. Strikingly, peptides derived from the CFEM domain of the haem-binding proteins Csa1, Pga10 and Rbt5 were capable of forming iron adduct ions during MS analysis, consistent with a key role of this domain in haem binding.

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Structural biology of heme binding in the Staphylococcus aureus Isd system

Cited by 129 publications

References 84 publications

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Electronic properties of the highly ruffled heme bound to the heme degrading enzyme IsdI

Iron restriction-induced adaptations in the wall proteome of Candida albicans

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