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Information on EC 3.4.21.91 - Flavivirin and Organism(s) Murray valley encephalitis virus and UniProt Accession P05769

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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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This record set is specific for:
Murray valley encephalitis virus
UNIPROT: P05769 not found.
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Word Map
The taxonomic range for the selected organisms is: Murray Valley encephalitis virus
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
-
NS2B-3 proteinase
-
-
-
-
Yellow fever virus (flavivirus) protease
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
154215-26-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Pyr-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
Pyr-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme is highly specific toward lysines at the P2 and P3 positions
-
-
?
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
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-Ala-Arg-agmatine
-
-
acetyl-Ala-Lys-agmatine
-
-
acetyl-Arg-Lys-agmatine
-
-
acetyl-Lys-Lys-agmatine
-
-
acetyl-Trp-Lys-agmatine
-
-
N2-(biphenyl-3-ylacetyl)-L-lysyl-N-[(1-carbamimidoylpiperidin-4-yl)methyl]-L-lysinamide
-
C-terminal agmatine peptidomimetic inhibitor, competitive
additional information
enzyme ligand binding structure analysis
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0025
N2-(biphenyl-3-ylacetyl)-L-lysyl-N-[(1-carbamimidoylpiperidin-4-yl)methyl]-L-lysinamide
-
pH 8.0, 25°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0471
acetyl-Ala-Arg-agmatine
Murray Valley encephalitis virus
-
pH 8.0, 25°C
0.0312
acetyl-Ala-Lys-agmatine
Murray Valley encephalitis virus
-
pH 8.0, 25°C
0.0237
acetyl-Arg-Lys-agmatine
Murray Valley encephalitis virus
-
pH 8.0, 25°C
0.0168
acetyl-Lys-Lys-agmatine
Murray Valley encephalitis virus
-
pH 8.0, 25°C
0.0268
acetyl-Trp-Lys-agmatine
Murray Valley encephalitis virus
-
pH 8.0, 25°C
0.0049
N2-(biphenyl-3-ylacetyl)-L-lysyl-N-[(1-carbamimidoylpiperidin-4-yl)methyl]-L-lysinamide
Murray Valley encephalitis virus
-
pH 8.0, 25°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
genome polyprotein; MVEV
UniProt
Manually annotated by BRENDA team
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
-
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of enzyme structures, PDB IDs 2V8O and 2WV9
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
Ang, M.J.; Yong, G.H.; Poulsen, A.; Then, S.W.; Li, Z.; Joy, J.; Hill, J.; Chia, C.S.
Substrate-based peptidomimetic inhibitors of the Murray Valley encephalitis virus NS2B/NS3 serine protease: a P1-P4 SAR study
Eur. J. Med. Chem.
68
72-80
2013
Murray Valley encephalitis virus
Manually annotated by BRENDA team
Ang, M.J.; Li, Z.; Lim, H.A.; Ng, F.M.; Then, S.W.; Wee, J.L.; Joy, J.; Hill, J.; Chia, C.S.
A P2 and P3 substrate specificity comparison between the Murray Valley encephalitis and West Nile virus NS2B/NS3 protease using C-terminal agmatine dipeptides
Peptides
52
49-52
2014
West Nile virus, Murray Valley encephalitis virus
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