Purification and characterization of the major iron-regulated protein expressed by pathogenic Neisseriae.

Mietzner, Timothy A.; Bolan, G; Schoolnik, Gary K.; Morse, Stephen

doi:10.1084/jem.165.4.1041

Cited by 60 publications

(54 citation statements)

References 36 publications

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“…S1 under "Supporting Information"). These profiles are similar to the FBP purified from gonococci by Mietzner et al (18). Crystallization trials were successful and confirmed the high purity of the protein.…”

Section: Overexpression and Characterization Of Nfbpsupporting

confidence: 65%

“…The synergistic anion binding properties of transferrins including their role in metal binding and release have been well documented (14 -16), but only recently have the synergistic anion binding properties of bacterial FBP been investigated (9,17). The FBP from N. gonorrhoeae (nFBP) has been biochemically characterized (18) and subsequently expressed in Escherichia coli (19,20). It has been reported that a large excess of NaHCO 3 increases the iron binding capacity of apo-FBP (21).…”

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confidence: 99%

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Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Guo

Harvey

Yang

et al. 2003

Journal of Biological Chemistry

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The 34-kDa periplasmic iron-transport protein (FBP) from Neisseria gonorrhoeae (nFBP) contains Fe(III) and (hydrogen)phosphate (synergistic anion). It has a characteristic ligand-to-metal charge-transfer absorption band at 481 nm. Phosphate can be displaced by (bi)carbonate to give Fe⅐CO 3 ⅐nFBP ( max 459 nm). The local structures of native Fe-PO 4 -nFBP and Fe⅐CO 3 ⅐nFBP were determined by EXAFS at the FeK edge using full multiple scattering analysis. The EXAFS analysis reveals that both phosphate and carbonate ligands bind to FBP in monodentate mode in contrast to transferrins, which bind carbonate in bidentate mode. The EXAFS analysis also suggests an alternative to the crystallographically determined position of the Glu ligand, and this in turn suggests that an H-bonding network may help to stabilize monodentate binding of the synergistic anion. The anions oxalate, pyrophosphate, and nitrilotriacetate also appear to serve as synergistic anions but not sulfate or perchlorate. The oxidation of Fe(II) in the presence of nFBP led to a weak Fe(III)⅐nFBP complex ( max 471 nm). Iron and phosphate can be removed from FBP at low pH (pH 4.5) in the presence of a large excess of citrate. Apo-FBP is less soluble and less stable than Fe⅐nFBP and binds relatively weakly to Ga(III) and Bi(III) but not to Co(III) ions, all of which bind strongly to apo-human serum transferrin.

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Section: Overexpression and Characterization Of Nfbpsupporting

confidence: 65%

mentioning

confidence: 99%

Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Guo

Harvey

Yang

et al. 2003

Journal of Biological Chemistry

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“…They both have the ability to reversibly bind ferric iron, and they share similar binding affinities (40). Also, only a single ferric ion binds per lobe (two for transferrin and one for FbpA), and the ferric iron-binding sites are similar (97,103). The crystal structure revealed that identical amino acid residues in transferrin and FbpA, i.e., two tyrosines, a histidine, and a glutamic acid, coordinate the iron atom but that these amino acids arise from different regions of FbpA than of transferrin (42).…”

Section: Transferrin and Lactoferrin Receptorsmentioning

confidence: 99%

“…FbpA is one of the major iron-regulated proteins and has been identified in all pathogenic Neisseria species (20,99,101). It has an apparent molecular mass of 37 kDa and is very basic (pI of Ͼ9.35) (97,98). The role of Fbp in the periplasmic transport of iron was first indicated by its localization to the periplasm and its transient association with 55 Fe acquired from 55 Fe-labeled human transferrin (19,40).…”

Section: Transferrin and Lactoferrin Receptorsmentioning

confidence: 99%

Iron Transport Systems in Neisseria meningitidis

Perkins-Balding

Ratliff-Griffin

Stojiljković

2004

Microbiol Mol Biol Rev

147

146

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SUMMARY Acquisition of iron and iron complexes has long been recognized as a major determinant in the pathogenesis of Neisseria meningitidis. In this review, high-affinity iron uptake systems, which allow meningococci to utilize the human host proteins transferrin, lactoferrin, hemoglobin, and haptoglobin-hemoglobin as sources of essential iron, are described. Classic features of bacterial iron transport systems, such as regulation by the iron-responsive repressor Fur and TonB-dependent transport activity, are discussed, as well as more specific features of meningococcal iron transport. Our current understanding of how N. meningitidis acquires iron from the human host and the vaccine potentials of various components of these iron transport systems are also reviewed.

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“…The gonococcal 37,000-dalton protein was purified by a combination of selective extraction with cetyltrimethylammonium bromide and column chromatography and used to produce both rabbit monospecific antiserum and murine monoclonal antibodies (39). Using these reagents, Mietzner et al (38) found that this protein was antigenically conserved among strains of N. gonorrhoeae, N. meningitidis, N. lactamica, and N. cinerea.…”

Section: Iron Metabolismmentioning

confidence: 99%

Physiology and metabolism of Neisseria gonorrhoeae and Neisseria meningitidis: implications for pathogenesis

et al. 1989

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Gonococci and meningococci are obligate human pathogens that can infect diverse sites within the human host. Each of these sites represents a unique niche with respect to nutrients, environmental factors, and competing microorganisms. The growth environment has a marked effect on the metabolism and cellular composition of Neisseria gonorrhoeae and N. meningitidis. Altered cellular composition is often reflected by changes in the cell surface that can ultimately affect the interaction of these microorganisms with the human host. The physiology and metabolism of the pathogenic Neisseria spp. have not been reviewed since 1979 (41). This review will discuss selected areas that have implications for the pathogenesis of these important microorganisms. IRON METABOLISMAfter entry into the human host, N. gonorrhoeae and N. meningitidis must multiply to colonize mucosal surfaces and to establish an infection. Cell growth and multiplication require essential nutrients such as iron. To obtain iron, the pathogenic Neisseria spp. must acquire it from the host. Despite the relative abundance of iron in the host, there is little free iron because of its sequestration by the ironbinding proteins transferrin (TF) and lactoferrin (LF) (19). In serum and interstitial fluid, iron is associated with TF; in breast milk, semen, and mucosal surfaces, it is associated primarily with LF. Consequently, gonococci and meningococci must possess mechanisms for utilizing the iron associated with the host iron-binding proteins as well as other potential in vivo iron sources such as heme and hemoglobin.Several studies have implicated iron in the virulence of the pathogenic Neisseria spp. Calver et al. (7) demonstrated that injection of ferrous sulfate prior to or injection of either iron sorbitol citrate or iron-dextran concomitantly with injection of N. meningitidis increased the lethality of several different meningococcal serogroups for mice by up to a 106-fold. The effect of the added iron was partially abrogated by the prior incubation of N. meningitidis with Desferal (CIBA-GEIGY Corp.), an iron chelator from which meningococci and gonococci are unable to remove iron (36). Holbein et al. (24) showed that the 50% lethal dose of N. meningitidis strains in a mouse model was decreased 109-fold by the concomitant administration of iron-dextran with the inoculum. Payne and Finkelstein (50) found that the intravenous inoculation of iron-containing compounds together with avirulent (nonpiliated) gonococci increased the lethality of these avirulent organisms for chicken embryos.Hafiz et al. (20) All strains of N. gonorrhoeae and N. meningitidis are able to grow with 25% iron-saturated TF as their sole source of iron (37). Archibald and DeVoe (1, 2) found that meningococci were capable of obtaining iron from a variety of iron-containing compounds including gastric mucin, ferric citrate, hemoglobin, myoglobin, and human TF. Iron complexed with a number of metabolic organic acids, polyphosphates, and several synthetic polycarboxylic acids was also re...

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Purification and characterization of the major iron-regulated protein expressed by pathogenic Neisseriae.

Cited by 60 publications

References 36 publications

Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Synergistic Anion and Metal Binding to the Ferric Ion-binding Protein from Neisseria gonorrhoeae

Iron Transport Systems in Neisseria meningitidis

Physiology and metabolism of Neisseria gonorrhoeae and Neisseria meningitidis: implications for pathogenesis

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