The "prismane" protein resolved: X-ray structure at 1.7 Å and multiple spectroscopy of two novel 4Fe clusters

Arendsen, A.F.; Hadden, Jonathan M.; Card, G.L.; McAlpine, A. S.; Bailey, Susan; Zaĭtsev, V. N.; Duke, Elizabeth H. M.; Lindley, P. F.; Kröckel, Monika; Trautwein, Alfred X.; Feiters, Martinus C.; Charnock, John; Garner, C. David; Marritt, Sophie J.; Thomson, Andrew J.; Kooter, Ingeborg M.; Johnson, Michael K.; Berg, W.A.M. van den; Dongen, W.M.A.M. van; Hagen, Wilfred R.

doi:10.1007/s007750050210

Cited by 68 publications

(50 citation statements)

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“…It is believed that Hcr transfers electrons from an unknown source to Hcp, which subsequently transfers the electrons to a substrate. The electron-accepting substrate of Hcp is unknown, although evidence from the crystal structure suggests that it is a diatomic molecule or smaller (1). Furthermore, the substrate is believed to be a gas, given the presence of hydrophobic solvent channels in the structure (5).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the genes are regulated by nitrite in Escherichia coli (44). Although the crystal structure of hcp has been solved (1,44), its substrates and reactions remain unidentified. The promoter region of pANI2 possessed homology to a region upstream of a hypothetical gene in E. coli, ytfE (89% amino acid identity with serovar Typhimurium, STM4399 in the LT2 sequence [26]).…”

Section: Isolation Of Acidified Nitrite-inducible Genesmentioning

confidence: 99%

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Modulation of Virulence by Two Acidified Nitrite-Responsive Loci ofSalmonella entericaSerovar Typhimurium

2003

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Two acidified nitrite-inducible genes of Salmonella enterica serovar Typhimurium were identified with a green fluorescent protein-based promoter-trap screen. The nitrite-inducible promoters were located upstream of loci that we designated nipAB and nipC, which correspond to hcp-hcr (hybrid cluster protein) of Escherichia coli and norA of Alcaligenes eutrophus, respectively. Maximal induction of the promoters by nitrite was dependent on pH. The nipAB promoter was regulated by oxygen in an Fnr-dependent manner. The nipC promoter was also regulated by oxygen but in an Fnr-independent manner. The promoters were upregulated in activated RAW264.7 macrophage-like cells, which produce NO via the inducible nitric oxide synthase (iNOS), and the induction was inhibited by aminoguanidine, an inhibitor of iNOS. Although the nipAB and nipC mutants displayed no defects under a variety of in vitro conditions or in tissue culture infections, they exhibited lower oral 50% lethal doses (LD 50 s) than did the wild type in C57BL/6J mouse infections. The lower LD 50 s reflected an unexpected increased ability of small inoculating doses of the mutant bacteria to cause lethal infection 2 to 3 weeks after challenge, compared to a similar challenge dose of wild-type bacteria. We conclude that these genes are regulated by physiological nitrogen oxides and that the absence of these bacterial genes in some way diminishes the ability of mice to clear a low dose infection.A hallmark of Salmonella enterica serovar Typhimurium (hereafter referred to as serovar Typhimurium) infection of the mouse is the presence of intracellular bacteria, primarily in macrophages, during all systemic phases of the disease (29,33). Macrophages ordinarily phagocytose particles and bacteria, which are then degraded in phagolysosomes by various means, including acid, cationic peptides, and oxidative radicals (18). In contrast, serovar Typhimurium is able to survive these challenges and exploit the macrophage as a site of intracellular replication and persistence. In order to circumvent or survive this hostile environment, serovar Typhimurium has evolved properties that allow it to avoid and persist in the presence of the innate and adaptive host immune systems.Reactive nitrogen intermediates (RNI) are also part of the arsenal of antibacterial measures produced by macrophages (13,18,35). Macrophages produce the inducible nitric oxide synthase (iNOS), which catalyzes the generation of nitric oxide (NO), upon stimulation with cytokines and/or mitogens. iNOS has been demonstrated to play a role in host defense from infection by a number of microbial agents, including serovar Typhimurium (25,34,45). While reactive oxygen intermediates seem to play a bactericidal role early during the infection process, NO displays a bacteriostatic effect at later time points (45), when most of the bacteria are intracellular. Although the localization of iNOS is not clear, recent work suggests that iNOS is present in multiple subcellular locations within macrophages (47). Furthermore, NO ...

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Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Acidified Nitrite-inducible Genesmentioning

confidence: 99%

Modulation of Virulence by Two Acidified Nitrite-Responsive Loci ofSalmonella entericaSerovar Typhimurium

2003

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“…Instead of having a typical [4Fe-4S] cluster, it has a [4Fe-2S-2O] cluster (Arendsen et al, 1998;van den Berg et al, 2000;Wolfe et al, 2002). According to dogma, Hcp is a hydroxylamine reductase that protects bacteria against the toxicity of hydroxylamine generated during nitrite reduction to ammonia.…”

Section: Repair Of Nitrosative Damagementioning

confidence: 99%

Legless pathogens: how bacterial physiology provides the key to understanding pathogenicity

Cole

2012

Microbiology

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“…HCPs are iron-sulfur proteins that contain two iron-sulfur clusters: one is either a conventional [2Fe-2S] or a cubane [4Fe-4S] cluster; the other is a hybrid [4Fe-4S-2O] cluster (2). HCPs are related to the carbon monoxide dehydrogenase protein family (16,31) and are widely distributed among obligate anaerobes and facultatively anaerobic bacteria.…”

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The NsrR Regulon of Escherichia coli K-12 Includes Genes Encoding the Hybrid Cluster Protein and the Periplasmic, Respiratory Nitrite Reductase

et al. 2007

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Successful pathogens must be able to protect themselves against reactive nitrogen species generated either as part of host defense mechanisms or as products of their own metabolism. The regulatory protein NsrR (a member of the Rrf2 family of transcription factors) plays key roles in this stress response. Microarray analysis revealed that NsrR represses nine operons encoding 20 genes in Escherichia coli MG1655, including the hmpA, ytfE, and ygbA genes that were previously shown to be regulated by NsrR. Novel NsrR targets revealed by this study include hcp-hcr (which were predicted in a recent bioinformatic study to be NsrR regulated) and the well-studied nrfA promoter that directs the expression of the periplasmic respiratory nitrite reductase. Conversely, transcription from the ydbC promoter is strongly activated by NsrR. Regulation of the nrf operon by NsrR is consistent with the ability of the periplasmic nitrite reductase to reduce nitric oxide and hence protect against reactive nitrogen species. Gel retardation assays were used to show that both FNR and NarL bind to the hcp promoter. The expression of hcp and the contiguous gene hcr is not induced by hydroxylamine. As hmpA and ytfE encode a nitric oxide reductase and a mechanism to repair iron-sulfur centers damaged by nitric oxide, the demonstration that hcp-hcr, hmpA, and ytfE are the three transcripts most tightly regulated by NsrR highlights the possibility that the hybrid cluster protein, HCP, might also be part of a defense mechanism against reactive nitrogen stress.

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The "prismane" protein resolved: X-ray structure at 1.7 Å and multiple spectroscopy of two novel 4Fe clusters

Cited by 68 publications

References 1 publication

Modulation of Virulence by Two Acidified Nitrite-Responsive Loci ofSalmonella entericaSerovar Typhimurium

Modulation of Virulence by Two Acidified Nitrite-Responsive Loci ofSalmonella entericaSerovar Typhimurium

Legless pathogens: how bacterial physiology provides the key to understanding pathogenicity

The NsrR Regulon of Escherichia coli K-12 Includes Genes Encoding the Hybrid Cluster Protein and the Periplasmic, Respiratory Nitrite Reductase

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