The molecular mechanism of interaction of trivalent dimethylarsinous acid (DMA^Ⅲ) binding to rat hemoglobin

In our previous work, we found that trivalent dimethylarsinous acid (DMA^Ⅲ) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA^Ⅲ has high binding affinity for Cys13 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA^Ⅲ with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA^Ⅲ binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA^Ⅲ from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA^Ⅲ, and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA^Ⅲ much easy to bind cysteine 13. Taken together, the DMA^Ⅲ specific binding to Cys13 is related to spatial structure of Cys13.