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Information on EC 3.4.21.91 - Flavivirin and Organism(s) Dengue virus type 4 and UniProt Accession Q2YHF0

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.91 Flavivirin
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Dengue virus type 4
UNIPROT: Q2YHF0 not found.
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Word Map
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Selective hydrolysis of -Xaa-Xaa-/-Yaa- bonds in which each of the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala
Synonyms
ns3 protease, nonstructural protein 3, ns2b-ns3 protease, ns3 serine protease, ns2b-ns3pro, ns2b/ns3 protease, ns3 proteinase, ns3pro, ns2b/ns3, zikv protease, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NS2B-NS3 protease-helicase
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NS2B18NS3
NS3 protein covalently attached to 18 residues of the N22B cofactor region
nonstructural protein 3
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NS2B-3 proteinase
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NS2B-NS3 protease
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Yellow fever virus (flavivirus) protease
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CAS REGISTRY NUMBER
COMMENTARY hide
154215-26-6
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP ATOO-647N + H2O
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show the reaction diagram
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affinity of complete NS3 molecule fused to 18 residues of the NS2B cofactor is 10fold higher than that of NS3 helicase
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ATP ATOO-647N + H2O
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show the reaction diagram
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affinity of complete NS3 molecule fused to 18 residues of the NS2B cofactor is 10fold higher than that of NS3 helicase
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?
additional information
?
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the recombinant NS2B-NS3 protease is subject to autolytic cleavage
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NS2B cofactor
N-terminal region of NS3 and its cofactor NS2B constitute the protease. To function as an active enzyme, the NS3 protease requires the NS2B cofactor. NS2B is an integral membrane protein of 14 kDa that contains three domains: two trans-membrane segments located at the N- and C-termini and a central region of 47 amino acids (spanning amino-acids 49-96) that acts as an essential protein cofactor of the NS3 protease
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NS2B protein
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
enzyme ligand binding structure analysis
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
the flavivirus NS3 protein is associated with the endoplasmic reticulum membrane via its close interaction with the central hydrophilic region of the NS2B integral membrane protein
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
the N-terminal region of NS3 and its cofactor NS2B constitute the protease that cleaves the viral polyprotein. The NS3 C-terminal domain possesses RNA helicase, nucleoside and RNA triphosphatase activities and is involved both in viral RNA replication and virus particle formation. NS2B-NS3 protein plays multiple roles in the virus life cycle. NS2B-NS3 serves as a hub for the assembly of the flavivirus replication complex and also modulates viral pathogenesis and the host immune response
additional information
enzyme ligand binding structure analysis, three-dimensional enzyme structure analysis
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
74000
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1 * 74000, SAXS experiments with the complete NS3 molecule fused to 18 residues of the NS2B cofactor
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
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1 * 74000, SAXS experiments with the complete NS3 molecule fused to 18 residues of the NS2B cofactor
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of enzyme structures, PDB IDs 2JLQ, 2JLR, 2JLU, 2JLV, 2JLW, 2JLX, 2JLY, 2JLZ, 2WHX, 2WZQ, and 2VBC
the identification of an alternative stable conformation for the full-length NS2B18NS3 protein is reported. In this second conformation refined to a resolution of 2.2 A, the protease domain has rotated by an angle of 161° relative to the helicase domain
complete NS3 molecule fused to 18 residues of the NS2B cofactor, by hanging-drop vapor diffusion method, at 3.15 A resolution. Protease domain sits beneath the ATP binding site, giving the molecule an elongated shape. Domain arrangement in the crystal structure fits into an envelope, suggesting a stable molecular conformation. A basic patch located at the surface of the protease domain increases the affinity for nucleotides and may also participate in RNA binding, explaining the higher unwinding activity of the full-length enzyme compared to that of the isolated helicase domain
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
mutation in the 11-amino acid linker region (169-179): a Gly residue before Pro174 is introduced in DENV4 NS2B18NS3: The mutant protein having a glycine insertion in its linker region adopts another conformation where the protease domain has not rotated by an angle of 161° relative to the helicase domain
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by anion-exchange chromatography
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complete NS3 molecule fused to 18 residues of the NS2B cofactor or NS3 helicase (residues 177 to 618) purified by gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
complete NS3 molecule fused to 18 residues of the NS2B cofactor or NS3 helicase (residues 177 to 618) cloned into pET32b vector and expressed in Escherichia coli BL21-CodonPlus
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plasmid pDV2-NS2B40-G4SG4-ASR-NS3FL expressed in Escherichia coli strain Rosetta2
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
flavivirus NS2B-NS3 protease-helicase is a target for antiviral drug development
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bera, A.K.; Kuhn, R.J.; Smith, J.L.
Functional characterization of cis and trans activity of the Flavivirus NS2B-NS3 protease
J. Biol. Chem.
282
12883-12892
2007
Japanese encephalitis virus, West Nile virus, Yellow fever virus, Dengue virus type 2, Dengue virus type 4, West Nile virus NY99
Manually annotated by BRENDA team
Luo, D.; Xu, T.; Hunke, C.; Grueber, G.; Vasudevan, S.G.; Lescar, J.
Crystal structure of the NS3 protease-helicase from dengue virus
J. Virol.
82
173-183
2008
Dengue virus type 4
Manually annotated by BRENDA team
Luo, D.; Wei, N.; Doan, D.N.; Paradkar, P.N.; Chong, Y.; Davidson, A.D.; Kotaka, M.; Lescar, J.; Vasudevan, S.G.
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
2010
Dengue virus type 2, Dengue virus type 4 (Q2YHF0)
Manually annotated by BRENDA team
Luo, D.; Vasudevan, S.G.; Lescar, J.
The flavivirus NS2B-NS3 protease-helicase as a target for antiviral drug development
Antiviral Res.
118
148-158
2015
Yellow fever virus (P03314), Murray Valley encephalitis virus (P05769), West Nile virus (P06935), Kunjin virus (P14335), dengue virus type I (P17763), Japanese encephalitis virus (P27395), Dengue virus type 2 (P29990), Dengue virus type 4 (Q2YHF0), Kokobera virus (Q32ZD5), Dengue virus type 3 (Q6YMS3), Dengue virus type 2 Thailand/16681/1984 (P29990), Dengue virus type 3 Martinique/1243/1999 (Q6YMS3), Yellow fever virus 17D vaccine (P03314), Dengue virus type 4 Thailand/0348/1991 (Q2YHF0), dengue virus type I Nauru/West Pac/1974 (P17763), Japanese encephalitis virus SA-14 (P27395), Kunjin virus MRM61C (P14335), Murray Valley encephalitis virus MVE-1-51 (P05769)
Manually annotated by BRENDA team