The binding regions of Luteolin with its potential target ribosomal protein S5

Weiqing Zhong, Lijuan Qiu, Chunlei Luo and Xin Meng

The binding regions of Luteolin with its potential target ribosomal protein S5

Weiqing Zhong, Lijuan Qiu, Chunlei Luo and Xin Meng

Second Military Medical University, China

: J Pharm Drug Deliv Res

Abstract

Liver fibrosis, a repairing response for the chronic liver injury from various pathogenesis, leads to the cirrhosis of liver. Many Chinese traditional drugs, such matrine and luteolin, have therapeutic efficacy on the liver fibrosis but the therapeutic mechanism is unknown. The activation of hepatic stellate cells (HSCs) is a critical course in the fibrosis and the ribosomal protein S5 (RPS5), a direct target of the anti-fibrotic agent MASM, could prevent HSC activation via the reduction of Akt phosphorylation. Our early study found that RPS5 could also be the target of luteolin. Here, we simulate the combination of RPS5 and luteolin by using the Discoverystudio4.0 to predict the binding sites of RPS5 with luteolin. The simulation shows that RPS5 have four binding regions with luteolin: the first region consists of Phe97 residue; the second region consists of Ans83, Lys85, and Arg159 residues; the third region consists of Arg127, Arg145, and Lys192 residues; and the forth region consists of Trp152, Arg159, and Glu160 residues. Mutation of these residues indicates that the Ans83 and Lys85 residues may be the major binding sites of RPS5 with luteolin. These results could provide a clue to the research on the anti-fibrotic mechanism of luteolin and the design of new drugs to inhibit the liver fibrosis.