Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2027658 | Steroids | 2015 | 9 Pages |
Abstract
The complex structure of human aromatase (CYP19) and the open form of ÎTGEE mutant NADPH-cytochrome P450 reductase (mCPR) was constructed using template-based protein alignment method. Dynamic simulation of formed complex was performed on NAMD 2.9, in which CHARMm all 27_prot_lipid_na force field and an explicit TIP3P water solvent model were applied. The result showed mCPR in its open conformation could steadily combine with aromatase from the proximal face. Data analysis indicates hydrogen bonds and four salt bridges on the binding surface enhance the interaction between the two protein molecules. Amino acid, Lys108 plays a key role in aromatase activity through the formation of a salt bridge with Asp147 and two hydrogen bonds with Asp147 and Gln150 in mCPR. The optimal pathway for the first electron transfer from CPR to aromatase was revealed and calculated using HARLEM software. The rates for solvent mediated and non-solvent mediated electron transfer from FMNH2 to heme were determined as 1.04Â ÃÂ 106Â sâ1 and 4.86Â ÃÂ 105Â sâ1 respectively, which indicates the solvent water can facilitate the electron transfer from FMNH2 to heme. This study presents a novel strategy for the study of the protein-protein interactions based on the template-based protein alignment, which may help new aromtase development targeting the electron transfer between mCPR and aromatase.
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Authors
Yuejie Dai, Jing Zhen, Xiuli Zhang, Yonghui Zhong, Shaodan Liu, Ziyue Sun, Yue Guo, Qingli Wu,