5Y6M

Zika virus helicase in complex with ADP-AlF3

Summary for 5Y6M

• Entry DOI: 10.2210/pdb5y6m/pdb
• Descriptor: Helicase domain from Genome polyprotein, MANGANESE (II) ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: zika viral helicase, hydrolysis, hydrolase
• Biological source: Zika virus (strain Mr 766) (ZIKV)
• Total number of polymer chains: 1
• Total formula weight: 49903.42

Authors

Yang, X.Y.,Chen, C.,Tian, H.L.,Chi, H.,Mu, Z.Y.,Zhang, T.Q.,Yang, K.L.,Zhao, Q.,Liu, X.H.,Wang, Z.F.,Ji, X.Y.,Yang, H.T. (deposition date: 2017-08-12, release date: 2018-07-04, Last modification date: 2023-11-22)

Primary citation

Yang, X.,Chen, C.,Tian, H.,Chi, H.,Mu, Z.,Zhang, T.,Yang, K.,Zhao, Q.,Liu, X.,Wang, Z.,Ji, X.,Yang, H.
Mechanism of ATP hydrolysis by the Zika virus helicase.
FASEB J., 32:5250-5257, 2018

PubMed Abstract: During its life cycle, Zika virus (ZIKV), an arthropod-borne flavivirus that is associated with Guillain-Barré syndrome and causes microencephaly in fetuses and newborn children, encodes a critical and indispensable helicase domain that has 5'-triphosphatase activity and performs ATP hydrolysis to generate energy and thus, sustains unwinding of double-stranded RNA during ZIKV genome replication. Of these processes, ATP hydrolysis represents the most basic event; however, its dynamic mechanisms remain largely unknown, impeding the further understanding of the function of ZIKV helicase and the ongoing anti-ZIKV drug design. In this work, we determined the crystal structure of ZIKV helicase in complex with ADP-AlF-Mn and ADP-Mn separately. The structural analysis indicates that these structures represent the intermediate state and posthydrolysis state, respectively, of the ATP hydrolysis process of ZIKV helicase. These findings, together with our earlier work, which identified the prehydrolysis state of ZIKV helicase, lead to a proposal of the ATP hydrolysis cycle for ZIKV helicase. On this basis, we used site-directed mutagenesis combined with an enzymatic study to identify successfully residues that are critical for the ATPase activity of ZIKV helicase; this will provide new ideas to understand the function for the key enzyme of ZIKV.-Yang, X., Chen, C., Tian, H., Chi, H., Mu, Z., Zhang, T., Yang, K., Zhao, Q., Liu, X., Wang, Z., Ji, X., Yang, H. Mechanism of ATP hydrolysis by the Zika virus helicase.

PubMed: 29913559
DOI: 10.1096/fj.201701140R

Experimental method

X-RAY DIFFRACTION (2.002 Å)