Browse > Article
http://dx.doi.org/10.13160/ricns.2018.11.2.121

Computational Analysis of Human Chemokine Receptor Type 6  

Sridharan, Sindhiya (Department of Genetic Engineering, School of Bioengineering, SRM University)
Saifullah, Ayesha Zainab (Department of Genetic Engineering, School of Bioengineering, SRM University)
Nagarajan, Santhosh Kumar (Department of Genetic Engineering, School of Bioengineering, SRM University)
Madhavan, Thirumurthy (Department of Genetic Engineering, School of Bioengineering, SRM University)
Publication Information
Journal of Integrative Natural Science / v.11, no.2, 2018 , pp. 121-129 More about this Journal
Abstract
CXCR6 is a major target in drug design as it is a determinant receptor in many diseases like AIDS, Type I Diabetes, some cancer types, atherosclerosis, tumor formation, liver disease and steatohepatitis. In this study, we propose the active site residues of CXCR6 molecule. We employed homology modelling and molecular docking approach to generate the 3D structure for CXCR6 and to explore its interaction between the antagonists and agonists. 3D models were generated using 14 different templates having high sequence identity with CXCR6. Surflex docking studies using pyridine and pyrimidine derivatives enabled the analysis of the binding site and finding of the important residues involved in binding. 3D structure of CXCL16, a natural ligand for CXCR6, was modelled using PHYRE and protein - protein docking was performed using ClusPro. The residues which were found to be crucial in interaction with the ligand are THR110, PHE113, TYR114, GLN160, GLN195, CYS251 and SER255. This study can be used as a guide for therapeutic studies of human CXCR6.
Keywords
CXCR6; Homology Modelling; Molecular Docking; CXCL16; Chemokines;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 L. Deng, N. Chen N, Y. Li, H. Zheng, and Q. Lei, "CXCR6/CXCL16 functions as a regulator in metastasis and progression of cancer", Biochim. Biophys. Acta, Vol. 1806, pp. 42-49, 2010.
2 E. Germanov, L. Veinotte, R. Cullen, E. Chamber-lain, E. C. Butcher, and B. Johnston, "Critical role for the chemokine receptor CXCR6 in homeostasis and activation of CD1d-restricted NKT cells", J. Immunol., Vol. 181, pp. 81-91, 2008.   DOI
3 A.Wehr, C. Baeck, F. Heymann, P. M. Niemietz, L. Hammerich, C. Martin, H. W. Zimmermann, O. Pack, N. Gassler, K. Hittatiya, A. Ludwig, T. Luedde, C. Trautwein, and F. Tacke, "Chemokine receptor CXCR6-dependent hepatic NK T cell tccu-mulation promotes inflammation and liver fibrosis", J. Immunol., Vol. 190, pp. 5226-5236, 2013.   DOI
4 C. Gunther, N. Carballido-Perrig, S. Kaesler, J. M. Carballido, and T. Biedermann, "CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells", J. Invest. Dermatol., Vol. 132, pp. 626-634, 2011.
5 B. J. Rabquer, P. S. Tsou, Y. Hou, E. Thirunavuk-karasu, G. K. Haines, A. J. Impens, K. Phillips, B. Kahaleh, J. R. Seibold, and A. E. Koch, "Dysregulated expression of MIG/CXCL9, IP-10/CXCL10 and CXCL16 and their receptors in systemic sclerosis", Arthritis Res. Ther., Vol. 13, p. R18, 2011.   DOI
6 L.-S. Ai and F. Liao, "Mutating the four extracel- lular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signalling", Biochemistry, Vol. 41, pp. 8332- 8341, 2002.   DOI
7 H. Nomiyama, N. Osada, and O. Yoshie, "Systematic classification of vertebrate chemokines based on conserved synteny and evolutionary history", Genes Cells, Vol. 18, pp. 1-16, 2012.
8 M. Thirumurthy, "Fragment based QSAR analysis of CXCR-2 inhibitors using topomer CoMFA approach", J. Chosun Natural Sci., Vol. 10, pp. 209- 215, 2017.
9 M. Wiederstein and M. J. Sippl, "ProSA-web: inter- active web service for the recognition of errors in three-dimensional structures of proteins", Nucleic Acids Res., Vol. 35, pp. W407-W410, 2007.   DOI
10 B. K. Kuntal, P. Aparoy, and P. Reddanna, "Easy-Modeller: a graphical interface to MODELLER", BMC Res. Notes, Vol. 3, pp. 226, 2010.   DOI
11 C. Colovos and T. O. Yeates, "Verification of protein structures: patterns of non-bonded atomic inter-actions", Protein Sci., Vol. 2, pp. 1511-1519, 1993.   DOI
12 S. C. Lovell, I. W. Davis, W. B. Arendall III, P. I. W. de Bakker, J. M. Word, M. G. Prisant, J. S. Richardson, and D. C. Richardson, "Structure validation by Ca geometry: f, y and Cb deviation", Proteins, Vol. 50, pp. 437-450, 2002.
13 J. Zhang, J. Romero, A. Chan, J. Goss, S. Stucka, J. Cross, B. Chamberlain, M. Varoglu, H. Chandon-net, D. Ryan, and B. Lippa, "Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease", Bioorg. Med. Chem. Lett., Vol. 25, pp. 3661-3664, 2015.   DOI
14 Sybyl - X 1.1, Tripos International, 1699 South Han-ley Road, St. Louis, MO, 63144-2319, USA, 2010.
15 J. Yang, R. Yan, A. Roy, D. Xu, J. Poisson, and Y. Zhang, "The I-TASSER Suite: protein structure and function prediction", Nat. Methods, Vol. 12, pp. 7-8, 2015.   DOI
16 L. A. Kelley, S. Mezulis, C. M. Yates, M. N. Wass, and M. J. E. Sternberg, "The Phyre2 web portal for protein modeling, prediction and analysis", Nat. Protoc., Vol. 10, pp. 845-858, 2015.   DOI
17 D. Kozakov, R. Brenke, S. Comeau, S. Vajda, "PIPER: An FFT-based protein docking program with pairwise potentials", Proteins, Vol. 65, pp. 392-406, 2006.   DOI
18 Z. Xiang, "Advances in homology protein structure modelling", Curr. Protein Pept. Sci., Vol. 7, pp. 217-227, 2006.   DOI
19 L. J. McGuffin, J. D. Atkins, B. R. Salehe, A. N. Shuid, and D. B. Roche, "IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences", Nucleic Acids Res., Vol. 43, pp. W169-W173, 2015.   DOI
20 S. K. Nagarajan and T. Madhavan, "Theoretical protein structure prediction of glucagon-like peptide 2 receptor using homology modelling", J. Chosun Natural Sci., Vol. 10, pp. 119-124, 2017.
21 K. A. Stegmann, F. Robertson, N. Hansi, U. Gill, C. Pallant, T. Christophides, L. J. Pallett, D. Peppa, C. Dunn, G. Fusai, V. Male, B. R. Davidson, P. Kennedy, and M. K. Maini, "CXCR6 marks a novel subset of T-betloEomeshi natural killer cells residing in human liver", Sci. Rep., Vol. 6, p. 26157, 2016.   DOI
22 S. Limou et al., "Multiple-cohort genetic association study reveals CXCR6 as a new chemokine receptor involved in long-term non-progression to AIDS", J. Infect. Dis., Vol. 202, pp. 908-915, 2015.
23 P. Duggal, P. An, T. H. Beaty, S. A. Strathdee, H. Farzadegan, R. B. Markham, L. Johnson, S. J. O'Brien, D. Vlahov, C. A. Winkler, "Genetic influence of CXCR6 chemokine receptor alleles on PCP-mediated AIDS progression among African Americans", Genes and Immun, vol. 4, pp. 245-50, 2003.   DOI
24 M. Matloubian, A. David, S. Engel, J. E. Ryan, and J. G. Cyster, "A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo", Nat. Immunol., Vol. 1, pp. 298-304, 2000.   DOI
25 S. M. Hald, Y. Kiselev, S. Al-Saad, E. Richardsen, C. Johannessen, M. Eilertsen, T. K. Kilvaer, K. Al-Shibli, S. Andersen, L. T. Busund, R. M. Bremnes, and T. Donnem, "Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer: com- bined high CXCL16 expression in tumor stroma and cancer cells yields improved survival", BMC Cancer, Vol. 15, p. 441, 2015.   DOI
26 M. M. Gaida, F. Gunther, C. Wagner, H. Friess, N. A. Giese, J. Schmidt, G. M. Hansch, and M. N. Wente, "Expression of the CXCR6 on polymorpho-nuclear neutrophils in pancreatic carcinoma and in acute, localized bacterial infections", Clin. Exp. Immunol., Vol. 154, pp. 216-223, 2008.   DOI