PDBsum entry 5k8l

Hydrolase

PDB id: 5k8l

Contents

Protein chain

443 a.a.

Ligands

EDO

GSP

MPD

Metals

_CL

Waters ×349

PDB id:

5k8l

Name:

Hydrolase

Title:

Crystal structure of zikv ns3 helicase in complex with gtp-gammar s

Structure:

Zikv ns3 helicase. Chain: a. Engineered: yes

Source:

Zika virus. Organism_taxid: 64320. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.75Å R-factor: 0.189 R-free: 0.240

Authors:

X.Cao,Y.Li,T.Jin

Key ref:

X.Cao et al. (2016). Molecular mechanism of divalent-metal-induced activation of NS3 helicase and insights into Zika virus inhibitor design. Nucleic Acids Res, 44, 10505-10514. PubMed id: 27915293

Date:

30-May-16 Release date: 09-Nov-16

Protein chain

A0A146CJG7  (A0A146CJG7_ZIKV) -  Genome polyprotein from Zika virus

Seq: 3423 a.a.

Struc: 443 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.3.4.21.91 - flavivirin.
• Reaction: Selective hydrolysis of Xaa-Xaa-|-Xbb bonds in which each of the Xaa can be either Arg or Lys and Xbb can be either Ser or Ala.
• Enzyme class 2: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺
• Enzyme class 3: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP (Bound ligand (Het Group name = GSP) matches with 90.91% similarity) + H2O = ADP + phosphate + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nucleic Acids Res 44:10505-10514 (2016)

PubMed id: 27915293

Molecular mechanism of divalent-metal-induced activation of NS3 helicase and insights into Zika virus inhibitor design.

X.Cao, Y.Li, X.Jin, Y.Li, F.Guo, T.Jin.

ABSTRACT

Zika virus has attracted increasing attention because of its potential for causing human neural disorders, including microcephaly in infants and Guillain-Barré syndrome. Its NS3 helicase domain plays critical roles in NTP-dependent RNA unwinding and translocation during viral replication. Our structural analysis revealed a pre-activation state of NS3 helicase in complex with GTPγS, in which the triphosphate adopts a compact conformation in the absence of any divalent metal ions. In contrast, in the presence of a divalent cation, GTPγS adopts an extended conformation, and the Walker A motif undergoes substantial conformational changes. Both features contribute to more extensive interactions between the GTPγS and the enzyme. Thus, this study provides structural evidence on the allosteric modulation of MgNTP^2-on the NS3 helicase activity. Furthermore, the compact conformation of inhibitory NTP identified in this study provides precise information for the rational drug design of small molecule inhibitors for the treatment of ZIKV infection.