Table 3.
In silico analysis of CYP2B6 (PDB ID: http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3IBD, UniProt: http://www.uniprot.org/uniprot/P20813; GenBank: NM_000767.5)
|
CYP2B6 Amino acid/mutation/alleles |
DUET ΔΔG, kcal/mol |
PopMusica ΔΔG, kcal/mol |
SAAFEC ΔΔG, kcal/mol |
MAESTROwebb ΔΔG, kcal/mol |
PolyPhen‐2 Score/mutation prediction |
MSAc aa conservation |
Involved in predicted ligand‐binding pockets/pocket No. (FTMap) | Involved in predicted or known channels | Involved in predicted PPI sites (meta‐PPISP) | Node degree (RING‐2.0) | Predicted fluctuation value (FlexPred) | Flexi‐bility classd (PredyFlexy) | Decreased metabolic activity or protein expression | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Gly99 G99E CYP2B6*12 |
−2.245 Destabilizing |
1.49 Destabilizing SA = 3.3% |
−0.491 Destabilizing |
0.025 Destabilizing Cpred = 0.924 |
1.000 Probably damaging |
High | No | Yes | No | 3 | 1.052 | 1 | Amino acid changes resulted in almost undetectable enzyme activity (in vitro) | Lang et al. (2004) |
|
Arg140 R140Q CYP2B6*14 |
−0.562 Destabilizing |
0.32 Destabilizing SA = 40.9% |
−3.798 Destabilizing |
0.471 Destabilizing Cpred = 0.786 |
0.020 Benign |
High | Yes/pocket 9 | No | Yes | 7 | 1.747 | 1 | Reduced expression and/or function activity of protein (in vitro) | Lang et al. (2004) |
|
Met198 M198T CYP2B6*27 |
−1.374 Destabilizing |
1.12 Destabilizing SA = 26.2% |
−0.580 Destabilizing |
−0.278 Stabilizing Cpred = 0.832 |
0.000 Benign |
High | Yes/pocket 1 | No | Yes | 10 | 1.223 | 0 | Loss‐of‐function allele *27 results in 85% decrease in enzyme activity. | Rotger et al. (2007) |
|
Ile391 I391N CYP2B6*15 |
−3.149 Destabilizing |
2.71 Destabilizing SA = 0.0% |
−1.012 Destabilizing |
0.992 Destabilizing Cpred = 0.890 |
1.000 Probably damaging |
High | No | No | No | 11 | 0.897 | 1 | Amino acid changes resulted in almost undetectable enzyme activity (in vitro) | Lang et al. (2004) |
For the program PopMusic solvent accessibility (SA) values are shown (in percent).
For the program MaestroWeb the confidence estimation Cpred is shown (0.0‐not reliable and 1.0‐highly reliable).
MSA‐Multiple sequence alignment.
Flexibility class was determined by the program PredyFlexy (rigid‐0, intermediate‐1, flexible‐2).
Wild‐type residue (bold).