Any feedback?
Please rate this page
(all_enzymes.php)
(0/150)

BRENDA support

3.4.21.91: Flavivirin

This is an abbreviated version!
For detailed information about Flavivirin, go to the full flat file.

Word Map on EC 3.4.21.91

Reaction

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

Dengue NS2b-NS3 protease, Dengue NS3 protease, dengue virus non-structural protein 3, dengue virus NS2B-NS3 protease, dengue virus protease, dengue virus serotype 2 protease, DENV NS2B-NS3, DENV-2 NS2B-NS3 protease, DENV2 NS2BNS3pro, DV2 NS2B/NS3pro, flavivirus NS2B-NS3 protease, non-structural protein 3 serine protease, non-structural protein NS2B-NS3 protease, nonstructural protein 3, NS2-3 protease, NS2B-3 proteinase, NS2B-NS3 complex, NS2B-NS3 protease, NS2B-NS3 protease-helicase, NS2B-NS3 proteinase, NS2B-NS3 proteolytic complex, NS2B-NS3 serine protease, NS2B-NS3 serine proteinase, NS2B-NS3(pro)teinase, NS2b-NS3-protease, NS2B-NS3p, NS2B-NS3pro, NS2B/3 protease, NS2B/NS3, NS2B/NS3 complex, NS2B/NS3 protease, NS2B/NS3 protease complex, NS2B/NS3 proteinase, NS2B/NS3 serine protease, NS2B/NS3pro serine protease, NS2B18NS3, NS2BNS3(pro)tease, NS3, NS3 protease, NS3 proteinase, NS3 serine protease, NS3pro, two-component NS2B-NS3 protease, viral serine protease NS2B/NS3, WNV NS2B-NS3, Yellow fever virus (flavivirus) protease, yellow fever virus NS2B-NS3-181 protease, YFV NS2B/NS3 protease, Zika protease, Zika virus NS2B-NS3 protease, ZIKV NS2B/NS3 protease, ZIKV protease

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.91 Flavivirin

Engineering

Engineering on EC 3.4.21.91 - Flavivirin

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
deltaV88
-
deletion mutant
G68A
-
substitution in the NS2B sequence, decreased activity compared with that of the wild-type enzyme
G81A
-
substitution in the NS2B sequence, decreased activity compared with that of the wild-type enzyme
L73A
-
substitution in the NS2B sequence, decreased activity compared with that of the wild-type enzyme
Q77A
-
substitution in the NS2B sequence, mutation has greater effects on substrate binding than on the reaction rate
V88D
-
reduced activity compared with that of the wild-type
V88K
-
reduced activity compared with that of the wild-type
W60A
-
substitution in the NS2B sequence, decreased activity compared with that of the wild-type enzyme
D129A
-
mutant shows 39fold reduction in catalytic efficacy compared to wild-type
D129E
-
no significant loss of activity
D129L
-
no significant loss of activity
D129R
-
no significant loss of activity
D129S
-
no significant loss of activity
G133A
-
mutant shows 10fold reduced catalytic activity
G148A
-
mutant exhibits impaired autolytic activity
G151A
-
inactive enzyme
I165A
-
mutant shows a drastic decrease in catalytic efficacy and a drastic increase in Km
K26A
-
mutant exhibits impaired autolytic activity
L115A
-
mutant shows activity comparable to wild-type
N152A
-
mutant shows no a complete inactivation but a 60fold reduced catalytic activity
S135A
S135C
-
almost inactive
S163A
-
mutant shows 12fold reduction in catalytic efficacy compared to wild-type
T134A
-
mutant shows 2.2fold reduction in catalytic efficacy compared to wild-type
Y150A
-
inactive enzyme
A125C/V162C
site-directed mutagenesis, the mutant shows 32% reduction in activity due to the cysteine substitution. Linked A125C/V162C, in which both mutations are within the protease domain, does not migrate differently without DTT. The unlinked either trap does not form intermolecular disulfide bonds
H51A
-
site-directed mutagenesis, the mutation of NS3 protein impairs the charge interaction and the pH dependence of the conformational changes. It stabilizes the open conformation, while the addition of BPTI still converts NS2B-NS3p from open to closed conformation
H51A/S75C
-
complex mutations
I73C/P106C
site-directed mutagenesis, the linked open trap mutant does not form intermolecular disulfide bonds appreciably, as evidenced by the lack of higher-molecular weight bands. Unlinked I73C/P106C forms a small amount of NS2BS-SNS3pro, which shows retarded migration as NS2B and NS3pro electrophorese as a single disulfide-bonded complex
K117A
site-directed mutagenesis
K117C
site-directed mutagenesis
K117R
site-directed mutagenesis
K117R/T122R
-
mutant is analyzed by 15N-HSQC spectra with and without inhibitor 4-guanidino-benzoic acid-4-nitrophenyl ester
K15A
-
autocleavage detected by SDS-PAGE is supressed
P176G
-
mutation in the 11-amino acid linker region (169-179): a 70% reduction in luciferase reporter signal and a similar reduction in the level of viral RNA synthesis are observed
S75C/K117C
site-directed mutagenesis, linked S75C/K117C is induced to form the NS2BS-SNS3pro closed conformation in the presence of active site inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride, suggesting that the mutation forms a disulfide bond when the enzyme is resting in the active conformation. The S75C/K117C pair is close together in the closed conformation but far apart in the open conformation and should therefore trap this variant in the closed conformation upon intramolecular disulfide bond formation
A125C/V162C
Dengue virus type 2 Thailand/16681/1984
-
site-directed mutagenesis, the mutant shows 32% reduction in activity due to the cysteine substitution. Linked A125C/V162C, in which both mutations are within the protease domain, does not migrate differently without DTT. The unlinked either trap does not form intermolecular disulfide bonds
-
I73C/P106C
Dengue virus type 2 Thailand/16681/1984
-
site-directed mutagenesis, the linked open trap mutant does not form intermolecular disulfide bonds appreciably, as evidenced by the lack of higher-molecular weight bands. Unlinked I73C/P106C forms a small amount of NS2BS-SNS3pro, which shows retarded migration as NS2B and NS3pro electrophorese as a single disulfide-bonded complex
-
K117A
Dengue virus type 2 Thailand/16681/1984
-
site-directed mutagenesis
-
S75C/K117C
Dengue virus type 2 Thailand/16681/1984
-
site-directed mutagenesis, linked S75C/K117C is induced to form the NS2BS-SNS3pro closed conformation in the presence of active site inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride, suggesting that the mutation forms a disulfide bond when the enzyme is resting in the active conformation. The S75C/K117C pair is close together in the closed conformation but far apart in the open conformation and should therefore trap this variant in the closed conformation upon intramolecular disulfide bond formation
-
C1123A
-
results in dramatic reductions in both auto-cleavage of the NS2/3 precursor and NS3 protease activities to levels that are close to the background of the assay
C1125A
-
results in dramatic reductions in both auto-cleavage of the NS2/3 precursor and NS3 protease activities to levels that are close to the background of the assay
C1171A
-
results in dramatic reductions in both auto-cleavage of the NS2/3 precursor and NS3 protease activities to levels that are close to the background of the assay
C1185A
-
has no effect on either auto-cleavage of the NS2/3 precursor and NS3 protease activities
C184A
-
mutation in the NS2 active site, is defective in NS2-3 processing. When Hepatitis C virus polyproteins with NS2 containing a C184A mutation are co-expressed, NS2 and NS3 cleavage products are detected
C922A
-
reduces NS2/3 auto-cleavage, but has no significant effect on NS3 protease activity
H1175A
-
reduces NS3 protease activity. Auto-cleavage activity is indistinguishable from wild-type
H143A
-
mutation in the NS2 active site, is defective in NS2-3 processing. When Hepatitis C virus polyproteins with NS2 containing a H143A mutation are co-expressed, NS2 and NS3 cleavage products are detected
H143A/C184A
-
mixing wild-type Flag-NS2-3 with double-mutant HA-NS2-3(H143A/C184A) or vice versa yields only cleaved wild-type NS2, whereas the double-mutant polypeptide remains unprocessed because neither of the composite active sites is functional, when a wild-type and a double-mutant NS2-3 dimerize
H952A
-
totally abolishes auto-cleavage of the NS2/3 precursor, whereas NS3 protease activity is not abolished
L1026P/A1027P
-
totally abolishes auto-cleavage of the NS2/3 precursor, whereas NS3 protease activity is not abolished
S1165A
-
completely abrogates NS3 protease activity, but has no effect on NS2/3 auto-cleavage
D42G
has no dramatic effect on either the catalytic activity (50% of wild-type) or self-proteolysis of NS2B-NS3pro. Aprotinin efficiently inhibits proteolytic activity
G460L
-
no autolytic cleavage, but is an efficient enzyme against the artificial substrate CFP-LQYTKRGGVLWD-YFP
P131K/T132P
-
decrease in kcat, which is partially compensated by an improvement in the substrate binding. Shift of the cleavage preferences toward that of the Dengue virus proteinase
S135A
D42G
-
has no dramatic effect on either the catalytic activity (50% of wild-type) or self-proteolysis of NS2B-NS3pro. Aprotinin efficiently inhibits proteolytic activity
-
G460L
-
no autolytic cleavage, but is an efficient enzyme against the artificial substrate CFP-LQYTKRGGVLWD-YFP
-
R76L
-
the mutant displays reduced catalytic efficiency compared to the wild type enzyme
-
S135A
-
no autolytic cleavage, is enzymatically inactive
-
T52V
-
the mutant displays increased catalytic efficiency compared to the wild type enzyme
-
S138A
-
is inactive towards Bz-Nle-Lys-Arg-Arg-7-amino-4-methylcoumarin
C143S
-
site-directed mutagenesis, the NS2B mutant cannot form the disulfide bond between C143 residues of neighboring NS3
R95*A/R29G
additional information