A crystal structure of the dengue virus non-structural protein 5 (NS5) polymerase delineates interdomain amino acid residues that enhance its thermostability and de novo initiation activities

Journal of Biological Chemistry

Volumn 288, Issue 43, 2013, Pages 31105-31114

  Lim, Siew Pheng ^a   Koh, Jolene Hong Kiew ^b   Seh, Cheah Chen ^a   Liew, Chong Wai ^c   Davidson, Andrew D ^b   Chua, Leng Shiew ^c   Chandrasekaran, Ramya ^c   Cornvik, Tobias C ^c   Shi, Pei Yong ^a   Lescar, Julien ^c,d  

^a NOVARTIS INSTITUTE FOR TROPICAL DISEASES   (Singapore)

^b UNIVERSITY OF BRISTOL   (United Kingdom)

^c NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

^d SORBONNE UNIVERSITÉ   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID RESIDUES; ASYMMETRIC UNIT; CATALYTIC PROPERTIES; ENZYMATIC ACTIVITIES; GLOBULAR DOMAINS; METHYLTRANSFERASES; ORTHORHOMBIC CRYSTALS; RNA-DEPENDENT RNA POLYMERASE;

AMINO ACIDS; MOLECULES; POLYMERS; RNA; SINGLE CRYSTALS; VIRUSES;

PROTEINS;

AMINO ACID; METHYLTRANSFERASE; NONSTRUCTURAL PROTEIN 5; RNA DIRECTED RNA POLYMERASE;

ARTICLE; CATALYSIS; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DENGUE VIRUS; ENZYME ACTIVITY; ENZYME CONFORMATION; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN STRUCTURE; RESIDUE ANALYSIS; STRUCTURE ANALYSIS; THERMOSTABILITY;

DENGUE VIRUS; ENZYME KINETICS; FLAVIVIRUS; FLAVIVIRUSES; LINKER REGION; NS5 PROTEIN; PROTEIN STABILITY; RNA-DEPENDENT RNA POLYMERASE; VIRAL POLYMERASE; X-RAY CRYSTALLOGRAPHY;

DENGUE VIRUS; ENZYME STABILITY; METHYLTRANSFERASES; MUTATION; PROTEIN STRUCTURE, TERTIARY; RNA REPLICASE; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84886647090     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.508606     Document Type: Article

References (28)

1. Davidson, A. D. (2009) New insights into flavivirus non-structural protein Adv. Virus Res. 74, 41-101
2. Noble, C. G., and Shi, P. Y. (2012) Structural biology of dengue virus enzymes: towards rational design of therapeutics. Antiviral Res. 96, 115-126
3. Sampath, A., and Padmanabhan, R. (2009) Molecular targets for flavivirus drug discovery. Antiviral Res. 81, 6-15
4. Malet, H., Massé, N., Selisko, B., Romette, J.-L., Alvarez, K., Guillemot, J.-C., Tolou, H., Yap, T. L., Vasudevan, S. G., Lescar, J., and Canard, B. (2008) The flavivirus polymerase as a target for drug discovery. Antiviral Res. 80, 23-35
5. Bussetta, C., and Choi, K. H. (2012) Dengue virus non-structural protein 5 adopts multiple conformations in solution. Biochemistry 51, 5921-5931
6. Yap, L. J., Luo, D., Chung, K. Y., Lim, S. P., Bodenreider, C., Noble, C., Shi, P.-Y., and Lescar, J. (2010) Crystal structure of dengue virus methyltransferase bound to a 5β-capped octameric RNA. PLoS One 5, e12836
7. Lim, S. P., Sonntag, L. S., Noble, C., Nilar, S. H., Ng, R. H., Zou, G., Monaghan, P., Chung, K. Y., Dong, H., Liu, B., Bodenreider, C., Lee, G., Ding, M., Chan, W. L., Wang, G., Yap, L. J., Chao, A. T., Lescar, J., Yin, Z., Vedananda, T. R., Keller, T. H., and Shi, P.-Y. (2011) Small-molecule inhibitors that selectively block dengue virus methyltransferase. J. Biol. Chem. 286, 6233-6240
8. Yap, T. L., Xu, T., Chen, Y. L., Malet, H., Egloff, M.-P., Canard, B., Vasudevan, S. G., and Lescar, J. (2007) The crystal structure of the Dengue virus RNA-dependent RNA polymerase at 1.85 Å resolution. J. Virol. 81, 4753-4765
9. Malet, H., Egloff, M. P., Selisko, B., Butcher, R. E., Wright, P. J., Roberts, M., Gruez, A., Sulzenbacher, G., Vonrhein, C., Bricogne, G., Mackenzie, J. M., Khromykh, A. A., Davidson, A. D., and Canard, B. (2007) Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5. J. Biol. Chem. 282, 10678-10689
10. Yap, T. L., Chen, Y. L., Xu, T., Wen, D., Vasudevan, S. G., and Lescar, J. (2007) A Multi-step strategy to obtain crystals of the dengue virus RNAdependent RNA polymerase that diffract to high resolution. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 63, 78-83
11. Noble, C. G., Lim, S. P., Chen, Y.-L., Liew, C. W., Yap, L., Lescar, J., and Shi, P.-Y. (2013) Conformational flexibility of the dengue virus RNA-dependentRNApolymerase revealed by a complex with an inhibitor. J. Virol. 87, 5291-5295
12. Niyomrattanakit, P., Chen, Y.-L., Dong, H., Yin, Z., Qing, M., Glickman, J. F., Lin, K., Mueller, D., Voshol, H., Lim, J. Y. H., Nilar, S., Keller, T. H., and Shi, P.-Y. (2010) Inhibition of dengue virus polymerase by blocking of the RNA tunnel. J. Virol. 84, 5678-5686
13. Hanley, K. A., Lee, J. J., Blaney, J. E., Jr., Murphy, B. R., and Whitehead, S. S. (2002) Paired charge-to-alanine mutagenesis of dengue virus type 4 NS5 generates mutants with temperature-sensitive, host range, and mouse attenuation phenotypes. J. Virol. 76, 525-531
14. Kroschewski, H., Lim, S. P., Butcher, R. E., Yap, T. L., Lescar, J., Wright, P. J., Vasudevan, S. G., and Davidson, A. D. (2008) Mutagenesis of the dengue virus type 2 NS5 methyltransferase domain. J. Biol. Chem. 283, 19410-19421
15. Leslie, A. (2006) The integration of macromolecular diffraction data. Acta Crystallogr. D Biol. Crystallogr. 62, 48-57
16. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr. DBiol. Crystallogr. 50, 760-763
17. Emsley, P., and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132
18. Pata, J. D., Schultz, S. C., and Kirkegaard, K. (1995) Functional oligomerization of poliovirus RNA-dependent RNA polymerase. RNA 1, 466-477
19. Wang, Q. M., Hockman, M. A., Staschke, K., Johnson, R. B., Case, K. A., Lu, J., Parsons, S., Zhang, F., Rathnachalam, R., Kirkegaard, K., and Colacino, J. M. (2002) Oligomerization and cooperative RNA synthesis activity of hepatitis C virus RNA-dependent RNA polymerase. J. Virol. 76, 3865-3872
20. Tellez, A. B., Wang, J., Tanner, E. J., Spagnolo, J. F., Kirkegaard, K., and Bullitt, E. (2011) Interstitial contacts in an RNA-dependent RNA polymerase lattice. J. Mol. Biol. 412, 737-750
21. Zou, G., Chen, Y.-L., Dong, H., Lim, C. C., Yap, L. J., Yau, Y. H., Shochat, S. G., Lescar, J., and Shi, P.-Y. (2011) Functional analysis of two cavities in flavivirus NS5 polymerase. J. Biol. Chem. 286, 14362-14372
22. Kapoor, M., Zhang, L., Ramachandra, M., Kusukawa, J., Ebner, K. E., and Padmanabhan, R. (1995) Association between NS3 and NS5 proteins of dengue virus type 2 in the putative RNA replicase is linked to differential phosphorylation of NS5. J. Biol. Chem. 270, 19100-19106
23. Egloff, M. P., Benarroch, D., Selisko, B., Romette, J. L., and Canard, B. (2002) AnRNAcap (nucleoside-2β-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J. 21, 2757-2768
24. Lu, G., and Gong, P. (2013) Crystal structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. PLoS Pathog. 9, e1003549
25. Luo, D., Wei, N., Doan, D. N., Paradkar, P. N., Chong, Y., Davidson, A. D., Kotaka, M., Lescar, J., and Vasudevan, S. G. (2010) Flexibility between the protease and helicase domains of the dengue virus NS3 protein conferred by the linker region and its functional implications. J. Biol. Chem. 285, 18817-18827
26. Assenberg, R., Mastrangelo, E., Walter, T. S., Verma, A., Milani, M., Owens, R. J., Stuart, D. I., Grimes, J. M., and Mancini, E. J. (2009) Crystal structure of a novel conformational state of the flavivirus NS3 protein: implications for polyprotein processing and viral replication. J. Virol. 83, 12895-12906
27. Welsch, S., Miller, S., Romero-Brey, I., Merz, A., Bleck, C. K., Walther, P., Fuller, S. D., Antony, C., Krijnse-Locker, J., and Bartenschlager, R. (2009) Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5, 365-375
28. Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P. A., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., Lopez, R., Thompson, J. D., Gibson, T. J., and Higgins, D. G. (2007) ClustalW and ClustalX version 2. Bioinformatics 23, 2947-2948