Citation: Kang Wenyuan, Xu Ximing, Guo Jianxiu, Tian Feifei. Molecular Dynamics Studies on the Structure of Aryl Hydrocarbon Receptor Fragment Affected by Site-Directed Mutagenesis[J]. Chemistry, ;2017, 80(2): 179-184, 207. shu

Molecular Dynamics Studies on the Structure of Aryl Hydrocarbon Receptor Fragment Affected by Site-Directed Mutagenesis

1.
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031
2.
Pathogenesis of Vascular Infections Unit, INSERM, Institut Pasteur, Paris 75015

Corresponding author: Tian Feifei, tulwar@home.swjtu.edu.cn
Received Date: 4 July 2016
Accepted Date: 26 August 2016

Figures(7)

The Aryl hydrocarbon receptor (AhR), a ligand-actived nuclear transcription factor, regulates the expressions of a diverse group of genes when small molecules go into the pocket of its single ligand binding domain(LBD). In this study, we found Phe289, Tyr316 and Ile319 play "gatekeeper" roles via comparing genus-species specific and structure analysis. The four mutation models (WT, Phe289Ala, Tyr316Ala, Ile319Ala) were performed using the Amber99sb force field of GROMACS software package. The complex stability, protein conformational change, active site volume and binding free energy of the binary complex were analyzed by "gatekeeper" residues function. The results indicated that Phe289, Tyr316 and Ile319 play "gatekeeper" roles through hydrophobic interaction. The whole structure analyses demonstrate that mutagenesis comes from the pockets, which will destabilize cavity environment, causing obvious fluctuations and leading to low ligand-affinity and ligand escape. These simulation results interpret some experimental phenomena and provide further structural information that are useful in drug design based on aryl hydrocarbon receptor.
- Molecular simulation,
- Molecular dynamics,
- Mutation,
- Aryl hydrocarbon receptor
1. [1]
  B W Smith, S S Rozelle, A Leung et al. Blood, 2013, 122:376~385. doi: 10.1182/blood-2012-11-466722
2. [2]
  P Y Chan-Hui, K Stephens, R A Warnock et al. Clin. Immunol., 2004, 111:162~174. doi: 10.1016/j.clim.2003.12.015
3. [3]
  A J Parks, M P Pollastri, M E Hahn et al. Mol. Pharmacol., 2014, 86:593~608. doi: 10.1124/mol.114.093369
4. [4]
  B Stockinger, P Di Meglio, M Gialitakis et al. Ann. Rev. Immunol., 2014, 32:403~432. doi: 10.1146/annurev-immunol-032713-120245
5. [5]
  J V Schmidt, C A Bradfield. Ann. Rev. Cell. Dev. Biol., 1996, 12:55~89. doi: 10.1146/annurev.cellbio.12.1.55
6. [6]
  P D Kottaridis, R E Gale, M E Frew et al. Blood, 2001, 98:1752~1759. doi: 10.1182/blood.V98.6.1752
7. [7]
  R J Kewley, M L Whitelaw, A Chapman-Smith. Int. J. Biochem. Cell Biol., 2004, 36:189~204. doi: 10.1016/S1357-2725(03)00211-5
8. [8]
  R Farmahin, G E Manning, D Crump et al. Toxicol. Sci., 2013, 131:139~152. doi: 10.1093/toxsci/kfs259
9. [9]
  A A Soshilov, M S Denison. Mol. Cell. Biol., 2014, 34:1707~1719. doi: 10.1128/MCB.01183-13
10. [10]
  A Pandini, A A Soshilov, Y Song et al. Biochemistry, 2009, 48:5972~5983. doi: 10.1021/bi900259z
11. [11]
  I Motto, A Bordogna, A A Soshilov et al. J. Chem. Inf. Model, 2011, 51:2868~2881. doi: 10.1021/ci2001617
12. [12]
  K Goryo, A Suzuki, C A del Carpio et al. Biochem. Biophys. Res. Commun., 2007, 354:396~402. doi: 10.1016/j.bbrc.2006.12.227
13. [13]
  J Key, T H Scheuermann, P C Anderson et al. J. Am. Chem. Soc., 2009, 131:17647~17654. doi: 10.1021/ja9073062
14. [14]
  M Bajpai. IDrugs, 2009, 12:174~185.
15. [15]
  M A Larkin, G Blackshields, N P Brown et al. Bioinformatics, 2007, 23:2947~2948. doi: 10.1093/bioinformatics/btm404
16. [16]
  M A Marti-Renom, A C Stuart, A Fiser et al. Ann. Rev. Biophys. Biomol. Struct., 2000, 29:291~325. doi: 10.1146/annurev.biophys.29.1.291
17. [17]
18. [18]
  N Tokuriki, F Stricher, J Schymkowitz et al. J. Mol. Biol., 2007, 369:1318~1332. doi: 10.1016/j.jmb.2007.03.069
19. [19]
  J A Maier, C Martinez, K Kasavajhala et al. J. Chem. Theory. Comput., 2015, 11:3696~3713. doi: 10.1021/acs.jctc.5b00255
20. [20]
  R Nuti, M Gargaro, D Matino et al. J. Chem. Inf. Model, 2014, 54:3373~3383. doi: 10.1021/ci5005459
21. [21]
  B Laurent, M Chavent, T Cragnolini et al. Bioinformatics, 2015, 31:1478~1480. doi: 10.1093/bioinformatics/btu822
22. [22]
  C S Bond, A W Schuttelkopf. Acta Crystallogr., Sect D:Biol. Crystallogr., 2009, 65:510~512. doi: 10.1107/S0907444909007835
23. [23]
  W Humphrey, A Dalke, K Schulten. J. Mol. Graphics, 1996, 14:33~38. doi: 10.1016/0263-7855(96)00018-5
24. [24]
  N Widderich, M Pittelkow, A Hoppner et al. J. Mol. Biol., 2014, 426:586~600. doi: 10.1016/j.jmb.2013.10.028
25. [25]
  A Unzue, H Zhao, G Lolli et al. J. Med. Chem., 2016, 59:3087~3097. doi: 10.1021/acs.jmedchem.5b01757
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沈阳化工大学材料科学与工程学院沈阳 110142