5GP1

Crystal structure of ZIKV NS5 Methyltransferase in complex with GTP and SAH

Summary for 5GP1

• Entry DOI: 10.2210/pdb5gp1/pdb
• Related: 5GOZ
• Descriptor: RNA-directed RNA polymerase NS5, SULFATE ION, P1-7-METHYLGUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: methyltransferase gtp complex, transferase
• Biological source: Zika virus (ZIKV)
• Total number of polymer chains: 3
• Total formula weight: 93478.48

Authors

Zhang, C.,Jin, T. (deposition date: 2016-07-30, release date: 2016-12-07, Last modification date: 2017-10-18)

Primary citation

Zhang, C.,Feng, T.,Cheng, J.,Li, Y.,Yin, X.,Zeng, W.,Jin, X.,Li, Y.,Guo, F.,Jin, T.
Structure of the NS5 methyltransferase from Zika virus and implications in inhibitor design
Biochem. Biophys. Res. Commun., 492:624-630, 2017

PubMed Abstract: Recent outbreak of flavivirus Zika virus (ZIKV) in America has urged the basic as well as translational studies of this important human pathogen. The nonstructural protein 5 (NS5) of the flavivirus has an N-terminal methyltransferase (MTase) domain that plays critical roles in viral RNA genome capping. The null mutant of NS5 MTase is lethal for virus. Therefore, NS5 is a potential drug target for the treatment of Zika virus infection. In this study, we determined crystal structures of the ZIKV MTase in complex with GTP and RNA cap analogue GpppA. Structural analyses revealed highly conserved GTP/cap-binding pocket and S-adenosylmethionine (SAM)-binding pocket. Two conformations of the second base of the cap were identified, which suggests the flexibility of RNA conformation. In addition, the ligand-binding pockets identified a continuous region of hotspots suitable for drug design. Docking calculation shows that the Dengue virus inhibitor compound 10 may bind to the ZIKV MTase.

PubMed: 27866982
DOI: 10.1016/j.bbrc.2016.11.098

Experimental method

X-RAY DIFFRACTION (2.444 Å)