Supplementary Material
A Theoretical Study on the Mechanism of a Superficial Mutation
Inhibiting the Enzymatic Activity of CYP1A2
Li-Na MA1,2, Zhen-Zhen DU3, Peng LIAN1, Dong-Qing WEI1
1(School of Life Science and Biotechnology, Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, P. R. China)
2(School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China)
3(Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P. R. China)
Fig. S1 The RMSD evolution of Cα atoms in WT_apo (black line) and F186L_apo (red line) with respect to the crystal structure of CYP1A2 (PDB ID: 2HI4).
Fig. S2 Distance between C13 atom of 7-ethoxyresorufin and the iron atom of the heme group. Ring numbers of 7-ethoxyresorufin are illustrated in red Roman numerals.
Fig. S3 MD simulations of wild-type and F186L. The type I binding mode was used for wild-type (a) and type II for F186L mutant (b). Panel c shows the RMSD evolution of Cα atoms in wild-type (black line) and F186L (red line) with respect to the crystal structure of CYP1A2 (PDB ID: 2HI4). The average structures of wild-type (gray) and F186L (colored) illustrate the same structural fold in two systems (d).
Table S1 The percentage of time that an access channel is open throughout the 6 ns stable MD simulation for the WT and the F186L mutant, estimated from Tables S2 and S3.
1 / 0 / 0
2a / 3% / 13%
2b / 3% / 0
2c / 43% / 10%
2d / 0 / 0
2e / 3% / 0
2f / 0 / 0
3 / 3% / 0
5 / 0 / 0
W / 0 / 0
S / 0 / 0
Table S2 Channel analysis of the wild-type CYP1A2. Open and closed channels are represented by blue and white rectangles for each snapshot extracted from the MD simulation, respectively.
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Table S3 Channel analysis of the F186L mutant CYP1A2. Open and closed channels are represented by blue and white rectangles for each snapshot extracted from the MD simulation, respectively.
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