Functional characterization of the dimerization domain of the ferric uptake regulator (Fur) of <i>Pseudomonas aeruginosa</i>

Bai, Erdeni; Rosell, Federico I.; Lige, Bao; Mauk, Marcia R.; Lelj-Garolla, Barbara; Moore, Geoffrey R.; Mauk, A. Grant

doi:10.1042/bj20061168

Cited by 5 publications

(12 citation statements)

References 44 publications

(70 reference statements)

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“…This is evident in the metal ion-amino acid distances in Table 1 and Fig. 4 did not find any zinc at close proximity to Cys132 or Cys137, in agreement with previous experimental reports for P. A. Fur [17,22] . From the metal ion-residue distances ( Fig.…”

Section: Resultssupporting

confidence: 92%

“…The Zn 2? ion was given the role of inducing and preserving the Fur dimer three dimensional structure [2,10,15,17,19,22]. Residues on the Fur dimer can be classified according to their sensitivity to metal ions as follows:…”

Section: Resultsmentioning

confidence: 99%

“…there are reports which state that Structural zinc is necessary yet insufficient for DNA binding [18]. In a recent report on P. A. Fur [22] the structural zinc was found to have lower stability constant (K A = 3.2 9 10 4 M -1 ), while the sensory binding site showed greater affinity towards Zn 2? with K A value of 5.7 9 10 6 M -1 ).…”

Section: Introductionmentioning

confidence: 96%

“…could replace Co 2? in the Fur structural zinc site [22]. In view of these reports, we studied the possibility of Fur binding to one Zn 2?…”

Section: Introductionmentioning

confidence: 99%

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Binding of the Zn2+ ion to ferric uptake regulation protein from E. coli and the competition with Fe2+ binding: a molecular modeling study of the effect on DNA binding and conformational changes of Fur

Jabour

Hamed

2008

J Comput Aided Mol Des

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The three dimensional structure of Ferric uptake regulation protein dimer from E. coli, determined by molecular modeling, was docked on a DNA fragment (iron box) and Zn(2+) ions were added in two steps. The first step involved the binding of one Zn2+ ion to what is known as the zinc site which consists of the residues Cys 92, Cys 95, Asp 137, Asp141, Arg139, Glu 140, His 145 and His 143 with an average metal-Nitrogen distance of 2.5 A and metal-oxygen distance of 3.1-3.2 A. The second Zn2+ ion is bound to the iron activating site formed from the residues Ile 50, His 71, Asn 72, Gly 97, Asp 105 and Ala 109. The binding of the second Zn2+ ion strengthened the binding of the first ion as indicated by the shortening of the zinc-residue distances. Fe2+, when added to the complex consisting of 2Zn2+/Fur dimer/DNA, replaced the Zn2+ ion in the zinc site and when a second Fe2+ was added, it replaced the second zinc ion in the iron activating site. The binding of both zinc and iron ions induced a similar change in Fur conformations, but shifted residues closer to DNA in a different manner. This is discussed along with a possible role for the Zn2+ ion in the Fur dimer binding of DNA in its repressor activity.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

“…could replace Co 2? in the Fur structural zinc site [22]. In view of these reports, we studied the possibility of Fur binding to one Zn 2?…”

Section: Introductionmentioning

confidence: 99%

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Binding of the Zn2+ ion to ferric uptake regulation protein from E. coli and the competition with Fe2+ binding: a molecular modeling study of the effect on DNA binding and conformational changes of Fur

Jabour

Hamed

2008

J Comput Aided Mol Des

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“…Bioinformatics analysis revealed that this protein comprises two conserved domains in the family of Fur/Zur proteins: a hypothetical DNA-binding motif at its N terminus and a putative C-terminal dimerizing module (2). Sensitivity assays with divalent transition metal ions demonstrated that gene 310 is a zinc-responsive regulator gene, referred to as zur (Fig.…”

Section: Discussionmentioning

confidence: 99%

Functional Definition and Global Regulation of Zur, a Zinc Uptake Regulator in a Streptococcus suis Serotype 2 Strain Causing Streptococcal Toxic Shock Syndrome

Feng

Zhang

et al. 2008

J Bacteriol

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Zinc is an essential trace element for all living organisms and plays pivotal roles in various cellular processes. However, an excess of zinc is extremely deleterious to cells. Bacteria have evolved complex machineries (such as efflux/influx systems) to control the concentration at levels appropriate for the maintenance of zinc homeostasis in cells and adaptation to the environment. The Zur (zinc uptake regulator) protein is one of these functional members involved in the precise control of zinc homeostasis. Here we identified a zur homologue designated 310 from Streptococcus suis serotype 2, strain 05ZYH33, a highly invasive isolate causing streptococcal toxic shock syndrome. Biochemical analysis revealed that the protein product of gene 310 exists as a dimer form and carries zinc ions. An isogenic gene replacement mutant of gene 310, the ⌬310 mutant, was obtained by homologous recombination. Physiological tests demonstrated that the ⌬310 mutant is specifically sensitive to Zn 2؉ , while functional complementation of the ⌬310 mutant can restore its duration capability, suggesting that 310 is a functional member of the Zur family. Two-dimensional electrophoresis indicated that nine proteins in the ⌬310 mutant are overexpressed in comparison with those in the wild type. DNA microarray analyses suggested that 121 genes in the ⌬310 mutant are affected, of which 72 genes are upregulated and 49 are downregulated. The transcriptome of S. suis serotype 2 with high Zn 2؉ concentrations also showed 117 differentially expressed genes, with 71 upregulated and 46 downregulated. Surprisingly, more than 70% of the genes differentially expressed in the ⌬310 mutant were the same as those in S. suis serotype 2 that were differentially expressed in response to high Zn 2؉ concentration, consistent with the notion that 310 is involved in zinc homeostasis. We thus report for the first time a novel zinc-responsive regulator, Zur, from Streptococcus suis serotype 2.Streptococcus suis 2 is a gram-positive pathogenic bacterium capable of infecting both piglets and humans and causing serious diseases such as arthritis, meningitis, and septicemia (58). It has spread to nearly 20 countries, resulting in more than 400 human cases of severe infection worldwide (38). In particular, two recent outbreaks (in 1998 and 2005) of severe human S. suis serotype 2 infections in China were characterized by streptococcal toxic shock syndrome, implying that highly invasive variants of S. suis serotype 2 might be emerging in Asia (63,72). Virulence factors related to the pathogenesis of S. suis serotype 2 have been partially elucidated and include capsular polysaccharide (56), suilysin (37), muraminidase-released protein (42), and extracellular factor (59). Very recently, our group (8) reported the whole genome sequences of two virulent S. suis serotype 2 isolates (05ZYH33 and 98HAH12).Similar to other transition metals such as iron, manganese,

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Effect of the amino acid substitution in the DNA-binding domain of the Fur regulator on production of pyoverdine

et al. 2012

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The ferric uptake regulator gene (fur), its promoter region and Fur box of pvdS gene involved in siderophore-mediated iron uptake system were sequenced in the parent strain Pseudomonas aeruginosa PAO1 and in the fur mutant FPA121 derived from the strain PAO1. We identified the gene fur 179 bearing a novel, single-point mutation that changed the amino acid residue Gln60Pro in the DNA-binding domain of the Fur protein. The synthesis of pyoverdine was studied in cultures of the strains PAO1 and FPA121 grown in iron-deplete and iron-replete (60 μmol/L FeIII) medium. The amino acid replacement in the regulatory Fur protein is responsible for the overproduction of pyoverdine in iron-deplete and iron-replete medium. No mutation was identified in the Fur box of the gene pvdS.

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Functional characterization of the dimerization domain of the ferric uptake regulator (Fur) of Pseudomonas aeruginosa

Cited by 5 publications

References 44 publications

Binding of the Zn2+ ion to ferric uptake regulation protein from E. coli and the competition with Fe2+ binding: a molecular modeling study of the effect on DNA binding and conformational changes of Fur

Binding of the Zn2+ ion to ferric uptake regulation protein from E. coli and the competition with Fe2+ binding: a molecular modeling study of the effect on DNA binding and conformational changes of Fur

Functional Definition and Global Regulation of Zur, a Zinc Uptake Regulator in a Streptococcus suis Serotype 2 Strain Causing Streptococcal Toxic Shock Syndrome

Effect of the amino acid substitution in the DNA-binding domain of the Fur regulator on production of pyoverdine

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