Arsenate Reductase of Staphylococcus aureus Plasmid pI258

Ji, Guangyong; Garber, Eric A. E.; Armes, Lyman G.; Chen, Chih‐Ming; Fuchs, James A.; Silver, Simón

doi:10.1021/bi00189a034

Cited by 131 publications

(135 citation statements)

References 16 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…Pentavalent arsenic is transported into cells via phosphate transport systems in both prokaryotes (5) and eukaryotes (6). It is reduced to the more toxic trivalent arsenite by arsenate reductases (7)(8)(9). Arsenite can be detoxified either by extrusion from cells or by sequestration within intracellular organelles as thiol conjugates (3,4,10).…”

mentioning

confidence: 99%

Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9

Liu

Shen

Carbrey

et al. 2002

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

459

298

View full text Add to dashboard Cite

Much is known about the transport of arsenite and antimonite into microbes, but the identities of mammalian transport proteins are unknown. The Saccharomyces cerevisiae FPS1 gene encodes a membrane protein homologous to the bacterial aquaglyceroporin GlpF and to mammalian aquaglyceroporins AQP7 and AQP9. Fps1p mediates glycerol uptake and glycerol efflux in response to hypoosmotic shock. Fps1p has been shown to facilitate uptake of the metalloids arsenite and antimonite, and the Escherichia coli homolog, GlpF, facilitates the uptake and sensitivity to metalloid salts. In this study, the ability of mammalian aquaglyceroporins AQP7 and AQP9 to substitute for the yeast Fps1p was examined. The fps1⌬ strain of S. cerevisiae exhibits increased tolerance to arsenite and antimonite compared to a wild-type strain. Introduction of a plasmid containing AQP9 reverses the metalloid tolerance of the deletion strain. AQP7 was not expressed in yeast. The fps1⌬ cells exhibit reduced transport of 73 As(III) or 125 Sb(III), but uptake is enhanced by expression of AQP9. Xenopus laevis oocytes microinjected with either AQP7 or AQP9 cRNA exhibited increased transport of 73 As(III). These results suggest that AQP9 and AQP7 may be a major routes of arsenite uptake into mammalian cells, an observation potentially of large importance for understanding the action of arsenite as a human toxin and carcinogen, as well as its efficacy as a chemotherapeutic agent for acute promyelocytic leukemia.Fps1p ͉ GlpF ͉ acute promyelocytic leukemia

show abstract

mentioning

confidence: 99%

Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9

Liu

Shen

Carbrey

et al. 2002

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

459

298

View full text Add to dashboard Cite

show abstract

“…Several families of ArsC have been identified and characterized (10 -14). Among these, Staphylococcus aureus ArsC has been extensively studied (8,(15)(16)(17)(18)(19)(20)(21). These studies revealed that three redox active cysteine residues (Cys 10 , Cys 82 , and Cys 89 ) are critical for arsenate reduction.…”

mentioning

confidence: 99%

“…The conserved CX 5 R anion-binding motif containing Cys 10 , known as the P-loop, is proposed to be the arsenate-binding site (23). Four cysteine residues (Cys 10 , Cys 15 , Cys 82 , and Cys 89 ) are conserved between the two ArsC proteins.…”

mentioning

confidence: 99%

Solution Structures and Backbone Dynamics of Arsenate Reductase from Bacillus subtilis

Guo

Peng

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Arsenate reductase encoded by the chromosomal arsC gene in Bacillus subtilis catalyzes the intracellular reduction of arsenate to arsenite, which is then extruded from cells through an efficient and specific transport system. Herein, we present the solution structures and backbone dynamics of both the reduced and oxidized forms of arsenate reductase from B. subtilis. The overall structures of both forms are similar to those of bovine low molecular weight protein-tyrosine phosphatase and arsenate reductase from Staphylococcus aureus. However, several features of the tertiary structure and mobility are notably different between the reduced and oxidized forms of B. subtilis arsenate reductase, particularly in the P-loop region and the segment Cys 82 -Cys 89 . The backbone dynamics results demonstrated that the reduced form of arsenate reductase undergoes millisecond conformational changes in the functional P-loop and Cys 82 -Cys 89 , which may facilitate the formation of covalent intermediates and subsequent reduction of arsenate. In the oxidized form, Cys 82 -Cys 89 shows motional flexibility on both picosecond-to-nanosecond and possibly millisecond time scales, which may facilitate the reduction of the oxidized enzyme by thioredoxin to regenerate the active enzyme. Overall, the internal dynamics and static structures of the enzyme provide insights into the molecular mechanism of arsenate reduction, especially the reversible conformational switch and changes in internal motions associated with the catalytic reaction.

show abstract

“…We have been able to successfully use the NPA-pKa correlation to determine the origin of the pKa perturbation of Nterminal cysteines in a-and 3 10 -helices, 12 in the study of the activation of the nucleophilic thiolates in the reaction catalyzed by arsenate reductase (ArsC) 13 and during mixed disulfide complex dissociation of ArsC and Trx. 11 In the conserved active site sequence motif Trp28-Cys29-Gly30-Pro31-Cys32 of Trx, we have studied the reactivity of Cys29 and Cys32 towards oxidized ArsC, 14,15 an endogenous substrate of Trx. Trx reduces oxidized ArsC via the formation of a mixed Trx-ArsC disulfide complex 16 (Fig.…”

Section: Introductionmentioning

confidence: 99%

The conserved active site tryptophan of thioredoxin has no effect on its redox properties

Roos¹,

Geerlings²,

Messens³

2009

Protein Science

View full text Add to dashboard Cite

In Staphylococcus aureus thioredoxin (Trx) it has been shown that mutation of the conserved active site tryptophan residue (Trp28) has a large effect on the protein stability, on the pKa of the nucleophilic cysteine and on the redox potential. Since these effects can either be due to the partially unfolding of the Trp28Ala mutant or to the absence of the indole side chain of Trp28 as possible interaction partner for the active site cysteines, the origin of the experimentally observed effects is not known and is beyond experimental approach. With theoretical pKa and density functional theory reactivity analysis on model systems where Trp28 has been replaced by an alanine within the structural environment of Trx it is shown that Trp28 does not affect the redox parameters of Trx. As such, the experimentally observed redox effects of the Trx W28A mutant might be due to structural changes induced by partial unfolding.

show abstract

Arsenate Reductase of Staphylococcus aureus Plasmid pI258

Cited by 131 publications

References 16 publications

Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9

Arsenite transport by mammalian aquaglyceroporins AQP7 and AQP9

Solution Structures and Backbone Dynamics of Arsenate Reductase from Bacillus subtilis

The conserved active site tryptophan of thioredoxin has no effect on its redox properties

Contact Info

Product

Resources

About