that binding of Arsenic to dithioglycerol, rescued cellular proteins

that arsenite can inhibit migration,there are also reports that show arsenic (37.5–375 ppb) inthe form of arsenic trioxide (As2O3) can reduce carcinogeniccell invasiveness in carcinogenic cell lines in part by downregulatingMMP-9 (15, 46, 53)

 

 

Arsenic binding to proteins

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The trivalent Arsenite has a tendency to bind to sulphydryl groups. The cysteine residues are a direct target of Arsenite in proteins and peptides. (Fig). The chemical reaction involved in Arsenic binding to cysteines has been well recognised. Some of the chemicals like arsine halides used in warfare during the first world war own their toxicity to their ability of binding to protein dithiols. To defy the toxic effects of such wafare agents, british government approved use of  ?-chlorovinyldichloroarsine (dithioglycerol) which has ability to form stable complexes with Arsenic. The competitive binding of Arsenic to dithioglycerol, rescued cellular proteins from binding to Arsenic. .61?63.

 

Arsenic affinity for proteins can result in conformational changes in the protein and loss of protein-protein and protein-DNA interactions. (Fig) Escherichia coli consists of a repressor protein ArsR in which each subunit within its ?-helix contains two cysteine residues. The unravelling of this ?-helix is required in order to accomidate trivalent Arsenite for binding to the protein. The unravelling of the helix causes the conformational change in the protein that dissocisates ArsR from DNA resulting in induction of gene expression.   Arsenite binds to three cysteine (Cys32, Cys34, andCys37) residues in ArsR, where Cys32 and Cys 37 is present in the  ?-helix of the DNA binding sites. The Cys residues in the protein are located in such a way that Arsenite is unable to bind unless the proteins unwinds for a conformational change. The other proteins  66,67

 

Arsenic Binding to Hemoglobin

Arsenic species are cleared from the blood immediately in humans, but the time of clearance of arsenic from animal species varies noticeably. The retention of arsenic is in rat and blood is longer when compared with other species.  Arsenic has been found to bind with transferring in hemodialysis patients. Haemoglobin in RBCs were predicted to be the sites of Arsenic accumulation, because haemoglobin constitutes 97% of dry weight of RBCs. The affinity of Haemoglobin in rat liver is much higher in Rats as compared with humans. The rat and human haemoglobin both consist of two chains of each ? and ?..Both hemoglobins are tetramers, each consisting of two ?-chains and two ?-chains. The difference lies in the number of the cysteine residues with rat haemoglobin consisting of three cysteines (Cys111,Cys13, and Cys104 ) in ?-chain while two cysteines (Cys125 and Cys93) in ?-chain. On the other hand human haemoglobin has only one cysteine in ?-chain and two cysteines in ?-chain.

 

 

 

Arsenic Binding to Other Proteins

Trivalent Arsenic species are also known to bind to other proteins like actin, tubulin, estrogen receptor and glucocorticoid receptors. Arsenite can bind to Kelch-like ECH-associated protein 1 (Keap 1). This is a major antioxidant sensing protein which acts at low Kd values. One of the most common motifs present in many proteins consists of two cysteine residues