Disease relevance of antimony hydroxide

• In Escherichia coli, the ArsAB pump provides resistance to arsenite and antimonite [1].
• Additional deletion of FPS1 in mutants defective in arsenite and antimonite detoxification partially suppresses their hypersensitivity to metalloid salts [2].
• We compared parental 2008 and A2780 human ovarian cancer cells to sublines selected for resistance to cisplatin (DDP) (2008/C8, 2008/C13*5.25, 2008/A, A2780/CP); we also compared 2008 cells to sublines selected for resistance to antimonite (2008/H) and arsenite (2008/I) which demonstrated cross-resistance to DDP [3].
• Here we show that the cyanobacterium Synechocystis sp. strain PCC 6803 contains an arsenic and antimony resistance operon consisting of three genes: arsB, encoding a putative arsenite and antimonite carrier, arsH, encoding a protein of unknown function, and arsC, encoding a putative arsenate reductase [4].
• Influence of antimonite, selenite, and mercury on the toxicity of arsenite in primary rat hepatocytes [5].

High impact information on antimony hydroxide

• 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 [6].
• As(GS)(3) transport by MRP1 was osmotically sensitive and was inhibited by several conjugated organic anions (MRP1 substrates) as well as the metalloid antimonite (K(i) 2.8 microM) [7].
• Antimonite elicits its effects by sequestering ArsA in the ArsA(1) conformation, which catalyzes rapid ATP hydrolysis at the A2 site to drive ArsA between conformations that have high (nucleotide-bound ArsA) and low affinity (nucleotide-free ArsA) for Sb(III) [8].
• Overall, the results are consistent with PGPA being an intracellular ABC transporter that confers arsenite and antimonite resistance by sequestration of the metal-thiol conjugates [9].
• On addition of antimonite, multisite catalysis involving both A1 and A2 sites occurs, resulting in a 40-fold increase in ATPase activity [10].

Chemical compound and disease context of antimony hydroxide

• The ATPase activity of ArsA, the catalytic subunit of the plasmid-encoded, ATP-dependent extrusion pump for arsenicals and antimonials in Escherichia coli, is allosterically activated by arsenite or antimonite [11].
• The same operon was also expressed in E. coli and conferred resistance to arsenite but less resistance to arsenate and antimonite [12].

Biological context of antimony hydroxide

• The transcription of the ars operon is negatively controlled by the ArsR repressor and induced by arsenite and antimonite [13].
• The A1 domain contains a high affinity ATP binding site, whereas the A2 domain has low affinity and it requires the allosteric ligand antimonite for binding ATP [10].
• The N-terminal amino acid sequence of the labeled fragment showed that FSBA binds preferentially to the C-terminal domain A2 both in the absence and the presence of antimonite [14].
• The results of previous transfection experiments in Leishmania had suggested that ltpgpA is only involved in low level resistance to arsenite and antimonite [15].
• ArsA possesses an allosteric site for antimonite [Sb(III)], the binding of which elevates the steady-state ATPase activity [16].

Anatomical context of antimony hydroxide

• In this study the influence of tetravalent selenite, trivalent antimonite, and divalent mercury was investigated in vitro using cultured primary rat hepatocytes [5].

Associations of antimony hydroxide with other chemical compounds

• The fps1Delta strain of S. cerevisiae exhibits increased tolerance to arsenite and antimonite compared to a wild-type strain [6].
• The ArsA protein, the catalytic component of the plasmid-encoded resistance system for removal of the toxic oxyanions arsenite, antimonite, and arsenate from bacterial cells, catalyzes oxyanion-stimulated ATP hydrolysis [17].
• In vitro, the organic arsenical was more effective than either arsenite or antimonite in dissociating the repressor-promoter complex [18].
• Capillary electrophoresis (CE) with indirect fluorescence detection was used to analyze selenium (selenite, selenate, selenomethionine, and selenocystine) and antimony (antimonite and antimonate) compounds [19].

Gene context of antimony hydroxide

• Arsenite or antimonite allosterically activates the ArsA ATPase activity [20].
• An internal deletion mutation in arsB resulted in decreased resistance to arsenate and total loss of arsenite and antimonite resistances [12].
• Thus antimonite binding may act as a switch in regulating ATP binding to A2 and hence the ATPase activity of ArsA [14].
• Extrapolation of the amount of FSBA required to inactivate the protein indicated that 1 mol of FSBA was sufficient to inhibit the activity of 1 mol of ArsA protein in the absence of substrates, while only 0.5 mol was required in the presence of the anionic substrate antimonite [17].
• In the presence of antimonite or arsenite the ArsR protein is released from the operator/ promoter region of the ars operon and beta-galactosidase is expressed [21].

References