Information on EC 3.4.23.B4 - Feline immunodeficiency virus protease

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The expected taxonomic range for this enzyme is: Feline immunodeficiency virus

EC NUMBER
COMMENTARY hide
3.4.23.B4
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
Feline immunodeficiency virus protease
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
the enzyme seems to have a preference for Val in P1' and Phe in P1. In contrast to the HIV-1 protease the feline immunodeficiency virus protease does not cleave the peptide KSGVFVQNGLVK at the Phe-Val bond. Gln in P2' may be inhibitory. In contrast to HIV-1 protease the feline immunodeficiency virus protease does not cleave peptide KSGNFVVNGLVK at the Phe-Val bond. Asn in P2 may be inhibitory
show the reaction diagram
The enzyme seems to have a preference for Val in P1' and Phe in P1. In contrast to the HIV-1 protease the feline immunodeficiency virus protease does not cleave the peptide KSGVFVQNGLVK at the Phe-Val bond. Gln in P2' may be inhibitory. In contrast to the HIV-1 protease the feline immunodeficiency virus protease does not cleave the peptide KSGNFVVNGLVK at the Phe-Val bond. Asn in P2 may be inhibitory
show the reaction diagram
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
144114-21-6
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ac-Lys-Ser-Gly-Val-Phe-Val-Val-Asn-Gly-Lys-NH2 + H2O
Ac-Lys-Ser-Gly-Val-Phe + Val-Val-Asn-Gly-Lys-NH2
show the reaction diagram
-
-
-
-
?
Ac-RPQAYPIQTR-NH2 + H2O
Ac-RPQAY + PIQTR-NH2
show the reaction diagram
Ac-RSQNYPIVQR-NH2 + H2O
Ac-RSQNY + PIVQR-NH2
show the reaction diagram
-
specific cleavage between Tyr and Pro, the peptide substrate represents the linking of Ma and CA proteins of the Gag region in the Gag-Pol polyprotein of HIV-1
-
-
?
Ala-Leu-Thr-(4-aminobenzoic acid)-Lys-Val-Gln-p-NO2-Phe-Val-Gln-Ser-Lys-Gly + H2O
Ala-Leu-Thr-(4-aminobenzoic acid)-Lys-Val-Gln + p-NO2-Phe-Val-Gln-Ser-Lys-Gly
show the reaction diagram
-
-
-
-
?
Ala-Leu-Thr-Lys-Val-Gln-Val-Val-Gln-Ser-Lys-Gly + H2O
Ala-Leu-Thr-Lys-Val-Gln + Val-Val-Gln-Ser-Lys-Gly
show the reaction diagram
Arg-Ala-Leu-Thr-Lys-(4-aminobenzoic acid)-Val-Gln-Phe-(NO2)-Val-Gln-Ser-Lys-Gly-Arg-NH2 + H2O
Arg-Ala-Leu-Thr-Lys-(4-aminobenzoic acid)-Val-Gln + Phe-(NO2)-Val-Gln-Ser-Lys-Gly-Arg-NH2
show the reaction diagram
-
-
-
?
Gag-Pol polyprotein + H2O
?
show the reaction diagram
Ile-Arg-Lys-Ile-Leu-Phe-Leu-Asp-Gly + H2O
Ile-Arg-Lys-Ile-Leu + Phe-Leu-Asp-Gly
show the reaction diagram
-
-
-
?
Lys-Gly-Ser-Gly-Ala-Leu-Thr-Asn-Ala-Val-Leu-Val-Pro-Lys + H2O
Lys-Gly-Ser-Gly-Ala-Leu-Thr-Asn + Ala-Val-Leu-Val-Pro-Lys
show the reaction diagram
-
-
-
?
Lys-Gly-Ser-Gly-Ala-Met-Val-Asn-Gln-Ala-Leu-Val-Pro-Lys + H2O
Lys-Gly-Ser-Gly-Ala-Met-Val-Asn + Gln-Ala-Leu-Val-Pro-Lys
show the reaction diagram
-
-
-
?
Lys-Gly-Ser-Gly-Gly-Arg-Ile-Asn-Val-Ala-Leu-Val-Pro-Lys + H2O
Lys-Gly-Ser-Gly-Gly-Arg-Ile-Asn + Val-Ala-Leu-Val-Pro-Lys
show the reaction diagram
-
-
-
?
Lys-Gly-Ser-Gly-Ile-Tyr-Thr-Val-Gln-Ser-Leu-Val-Pro-Lys + H2O
Lys-Gly-Ser-Gly-Ile-Tyr + Thr-Val-Gln-Ser-Leu-Val-Pro-Lys
show the reaction diagram
-
-
-
-
?
Lys-Gly-Ser-Gly-Leu-Thr-Met-Val-Thr-Gln-Leu-Val-Pro-Lys + H2O
Lys-Gly-Ser-Gly-Leu-Thr-Met + Val-Thr-Gln-Leu-Val-Pro-Lys
show the reaction diagram
-
-
-
-
?
Lys-Gly-Ser-Gly-Thr-Trp-Met-Val-His-Ser-Leu-Val-Pro-Lys + H2O
Lys-Gly-Ser-Gly-Thr-Trp + Met-Val-His-Ser-Leu-Val-Pro-Lys
show the reaction diagram
-
-
-
?
Lys-Gly-Ser-Gly-Val-Phe-Ala-Val-Thr-Gln-Leu-Val-Pro-Lys + H2O
Lys-Gly-Ser-Gly-Val-Phe + Ala-Val-Thr-Gln-Leu-Val-Pro-Lys
show the reaction diagram
-
-
-
?
Lys-Gly-Ser-Gly-Val-Tyr-Gln-Leu-Ser-Ala-Leu-Val-Pro-Lys
?
show the reaction diagram
-
two cleavage sites: Tyr-Gln and Leu-Ser
-
-
?
Lys-Ser-Gly-Ile-Phe-Val-Val-Asn-Gly-Leu-Val-Lys + H2O
Lys-Ser-Gly-Ile-Phe + Val-Val-Asn-Gly-Leu-Val-Lys
show the reaction diagram
-
-
-
?
Lys-Ser-Gly-Val-Phe-His-Val-Asn-Gly-Lys + H2O
Lys-Ser-Gly-Val-Phe + His-Val-Asn-Gly-Lys
show the reaction diagram
-
-
-
?
Lys-Ser-Gly-Val-Phe-Ser-Val-Asn-Gly-Leu-Val-Lys + H2O
Lys-Ser-Gly-Val-Phe + Ser-Val-Asn-Gly-Leu-Val-Lys
show the reaction diagram
-
-
-
?
Lys-Ser-Gly-Val-Phe-Val-Val-Asn-Gly-Leu-Val-Lys + H2O
Lys-Ser-Gly-Val-Phe + Val-Val-Asn-Gly-Leu-Val-Lys
show the reaction diagram
-
-
-
?
Lys-Ser-Gly-Val-Phe-Val-Val-Asn-Gly-Lys + H2O
Lys-Ser-Gly-Val-Phe + Val-Val-Asn-Gly-Lys
show the reaction diagram
-
-
-
-
?
Lys-Ser-Gly-Val-Phe-Val-Val-Gln-Gly-Leu-Val-Lys + H2O
Lys-Ser-Gly-Val-Phe + Val-Val-Gln-Gly-Leu-Val-Lys
show the reaction diagram
-
-
-
?
Lys-Ser-Gly-Val-Phe-Val-Val-Thr-Gly-Leu-Val-Lys + H2O
Lys-Ser-Gly-Val-Phe + Val-Val-Thr-Gly-Leu-Val-Lys
show the reaction diagram
-
-
-
?
Lys-Ser-Phe-Val-Phe-Val-Val-Asn-Gly-Leu-Val-Lys + H2O
Lys-Ser-Phe-Val-Phe + Val-Val-Asn-Gly-Leu-Val-Lys
show the reaction diagram
-
-
-
?
RALTK(epsilon-ABZ)VQF(NO2)VQSKGR + H2O
RALTK(epsilon-ABZ)VQ + F(NO2)VQSKGR
show the reaction diagram
-
the synthetic peptide substrate mimicks the capsid/nucleocapsid cleavage site
-
-
?
RKEEGPPQAYPIQTVNGPQYR + H2O
RKEEGPPQAY + PIQTVNGPQYR
show the reaction diagram
-
the addition of Arg at the ends of the peptides subtrate increases the solubility, specific cleavage between Tyr and Pro, the peptide mimicks the linking of Ma and CA proteins of the Gag region in the Gag-Pol polyprotein in HIV-1
-
-
?
Thr-Ile-Met-Met-Gln-Arg + H2O
Thr-Ile-Met + Met-Gln-Arg
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Gag-Pol polyprotein + H2O
?
show the reaction diagram
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NaCl
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increasing salt concentration up to 1.5 M increases the enzyme activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1-[1-[1-(4-[2-[2-(2-Benzyloxycarbonylamino-3-hydroxy-propionylamino)-propionylamino]-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butylcarbamoyl)-2-methyl-propylcarbamoyl]-ethylcarbamoyl]-2-hydroxy-ethyl)-carbamic acid benzyl ester
-
IC50: 128 nM
(3S,4R,5R,6S)-3,4-di-O-(3'-fluorobenzyl)-N-methyl-3,4,5,6-tetrahydroxyazepane N-oxide
-
weak
(3S,4R,5R,6S)-3,6-di-O-(3',5'-difluorobenzyl)-3,4,5,6-tetrahydroxyazepane
-
IC50: 0.67 mM
(3S,4R,5R,6S)-3,6-di-O-(3'-fluorobenzyl)-3,4,5,6-tetrahydroxyazepane
-
IC50: 1.4 mM
2-(2-Benzenesulfonylamino-propionylamino)-N-[4-[2-(2-benzenesulfonylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butyl]-3-methyl-butyramide
-
IC50: 138 nM
2-[2-(4-Bromo-benzenesulfonylamino)-propionylamino]-N-(4-[2-[2-(4-bromo-benzenesulfonylamino)-propionylamino]-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butyl)-3-methyl-butyramide
-
IC50: 141 nM
2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-N-(4-[2-[2-acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-1-benzyl-2,3-dihydroxy-5-phenyl-pentyl)-3-methyl-butyramide
-
IC50: 212 nM
3-(2-Hydroxy-3-[2-[2-(hydroxy-methyl-amino)-3-phenyl-propionylamino]-3-methyl-butyrylamino]-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
-
IC50: 48 nM
3-(2-Hydroxy-3-[2-[2-(hydroxy-methyl-amino)-3-phenyl-propionylamino]-3-methyl-butyrylamino]-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (3-methyl-2-methylamino-butyryl)-amide
-
IC50: 117 nM
3-(2-Hydroxy-3-[2-[2-(hydroxy-methyl-amino)-propionylamino]-3-methyl-butyrylamino]-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
-
IC50: 182 nM
3-(3-[2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-2-hydroxy-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
-
IC50: 256 nM
3-(3-[2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-2-hydroxy-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (3-methyl-2-methylamino-butyryl)-amide
-
IC50: 80 nM
3-(3-[2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-2-hydroxy-4-phenyl-butyryl)-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
-
IC50: 0.0012 mM
Ac-Gly-Ser-Gly-Val-Phe-Psi[CH2NH2]-Val-Val-Asn-Gly-Leu
-
-
Ac-GSGVFPSI[CH2NH]VVNGL-NH2
-
strong inhibition of FIV retropepsin
Ac-naphthylalanine-Val-statine-Glu-naphthylalanine-NH2
-
an inhibitor derived from aspartic proteinase inhibitors, statine is 3-hydroxy-4-amino-7-methylheptanoic acid
Gly-Ser-Gly-Val-Phe[CH2NH]-Val-Val-Asn-Gly-Leu
-
IC50: 0.0004 mM
Gly-Ser-Gly-Val-Phe[CHOHCH2]-Val-Val-Asn-Gly-Leu
-
IC50: 0.005 mM
LP-149
N-(2,3-Dihydroxy-4-[2-[2-(4-methoxy-benzenesulfonylamino)-propionylamino]-3-methyl-butyrylamino]-1,4-diphenyl-butyl)-2-[2-(4-methoxy-benzenesulfonylamino)-propionylamino]-3-methyl-butyramide
-
IC50: 310 nM
N-(2,3-Dihydroxy-4-[3-methyl-2-[2-(3-p-tolyl-ureido)-propionylamino]-butyrylamino]-1,4-diphenyl-butyl)-3-methyl-2-[2-(3-p-tolyl-ureido)-propionylamino]-butyramide
-
IC50: 0.2 mM
N-(2,3-Dihydroxy-4-[3-methyl-2-[2-(toluene-4-sulfonylamino)-propionylamino]-butyrylamino]-1,4-diphenyl-butyl)-3-methyl-2-[2-(4-methyl-cyclohexa-1,3-dienesulfonylamino)-propionylamino]-butyramide
-
IC50: 17 nM
N-(2,3-Dihydroxy-4-[3-methyl-2-[2-(toluene-4-sulfonylamino)-propionylamino]-butyrylamino]-1,4-diphenyl-butyl)-3-methyl-2-[2-(4-nitro-cyclohexa-1,3-dienesulfonylamino)-propionylamino]-butyramide
-
IC50: 228 nM
N-[1-(1-[2,3-Dihydroxy-4-[3-methyl-2-(2-nicotinylamino-propionylamino)-butyrylamino]-1,4-diphenyl-butylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-nicotinamide
-
62 nM
N-[1-(1-[4-[2-(2-Benzoylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-benzamide
-
IC50: 156 nM
N-[2,3-Dihydroxy-4-(2-[2-[3-(4-methoxy-phenyl)-ureido]-propionylamino]-3-methyl-butyrylamino)-1,4-diphenyl-butyl]-2-[2-[3-(4-methoxy-phenyl)-ureido]-propionylamino]-3-methyl-butyramide
-
IC50: 0.2 mM
N-[2,3-Dihydroxy-4-(3-methyl-2-[2-[3-(4-trifluoromethoxy-phenyl)-ureido]-propionylamino]-butyrylamino)-1,4-diphenyl-butyl]-3-methyl-2-[2-[3-(4-trifluoromethoxy-phenyl)-ureido]-propionylamino]-butyramide
-
IC50: 0.119 mM
N-[2,3-Dihydroxy-4-(3-methyl-2-[2-[3-(4-trifluoromethyl-phenyl)-ureido]-propionylamino]-butyrylamino)-1,4-diphenyl-butyl]-3-methyl-2-[2-[3-(4-trifluoromethyl-phenyl)-ureido]-propionylamino]-butyramide
-
IC50: 0.2 mM
N-[2,3-Dihydroxy-4-[3-methyl-2-(2-phenylmethanesulfonylamino-propionylamino)-butyrylamino]-1,4-diphenyl-butyl]-3-methyl-2-(2-phenylmethanesulfonylamino-propionylamino)-butyramide
-
IC50: 118 nM
N-[benzyloxycarbonyl]-L-Ala-N-[(1S)-1-benzyl-2-hydroxyethyl]-L-valinamide
-
ie. TL-3
protease inhibitor AB-2
-
a HIV-1 protease inhibitor, IC50: 0.0011 mM
protease inhibitor AB-6
-
a HIV-1 protease inhibitor, IC50: 0.001 mM
protease inhibitor AB-8
-
a HIV-1 protease inhibitor, IC50: 0.008 mM
protease inhibitor APV-1
-
a HIV-1 protease inhibitor, IC50: 0.001 mM
protease inhibitor RTV
-
a HIV-1 protease inhibitor, weak inhibition of wild-type FIV protease, IC50: 0.045 mM
protease inhibitor TL-3
saquinovir
-
weak inhibition of wild-type protease
[(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-acetylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-methyl]-carbamic acid benzyl ester
-
-
[1-(1-[1-Benzyl-2,3,3-trihydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-propylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
-
IC50: 200 nM
[1-(1-[1-Benzyl-2-hydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-3-oxo-propylcarbamoyl]-2-methyl-propylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-carbamic acid benzyl ester
-
IC50: 0.001 mM
[1-(1-[1-Benzyl-2-hydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-3-oxo-propylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
-
IC50: 0.019 mM
[1-(1-[1-Benzyl-2-hydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-propylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
-
IC50: 0.0052 mM
[1-(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-2-phenyl-ethyl]-carbamic acid benzyl ester
-
; IC50: 0.0092
[1-(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester
-
-
[1-(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
-
-
[1-(1-[4-[2-(2-Benzyloxycarbonylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
-
IC50: 100 nM
[1-[1-(1-Benzyl-3-[4-[2-(2-benzyloxycarbonylamino-propionylamino)-3-methyl-butyrylcarbamoyl]-5,5-dimethyl-thiazolidin-3-yl]-2,3,3-trihydroxy-propylcarbamoyl)-2-methyl-propylcarbamoyl]-ethyl]-carbamic acid benzyl ester
-
IC50: 95 nM
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0056 - 0.271
Ala-Leu-Thr-Lys-Val-Gln-Val-Val-Gln-Ser-Lys-Gly
0.013
Arg-Ala-Leu-Thr-Lys-(4-aminobenzoic acid)-Val-Gln-Phe-(NO2)-Val-Gln-Ser-Lys-Gly-Arg-NH2
-
-
0.462 - 1.845
Ile-Arg-Lys-Ile-Leu-Phe-Leu-Asp-Gly
0.033
RALTK(epsilon-ABZ)VQF(NO2)VQSKGR
-
pH 5.3, 0.2 M NaCl, 0.1 mM EDTA, 1 mM DTT
10
RKEEGPPQAYPIQTVNGPQYR
-
pH 5.3, 37°C, 1 M NaCl
additional information
additional information
-
Km-values for multiple-substitution mutants constructed by replacing the residues in and around the active site of the enzyme with structurally equivalent residues of HIV-1 protease
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0015 - 3.01
Ala-Leu-Thr-Lys-Val-Gln-Val-Val-Gln-Ser-Lys-Gly
0.11
Arg-Ala-Leu-Thr-Lys-(4-aminobenzoic acid)-Val-Gln-Phe-(NO2)-Val-Gln-Ser-Lys-Gly-Arg-NH2
feline immunodeficiency virus
-
-
0.945 - 4
Ile-Arg-Lys-Ile-Leu-Phe-Leu-Asp-Gly
0.29
RALTK(epsilon-ABZ)VQF(NO2)VQSKGR
feline immunodeficiency virus
-
pH 5.3, 0.2 M NaCl, 0.1 mM EDTA, 1 mM DTT
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00026
Ac-naphthylalanine-Val-statine-Glu-naphthylalanine-NH2
-
-
0.076
Ro31-8959
-
pH 5.25, 37°C
0.000156
[(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-acetylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-methyl]-carbamic acid benzyl ester
-
-
0.007
[1-(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-2-phenyl-ethyl]-carbamic acid benzyl ester
-
-
0.000159
[1-(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-3-methyl-butyl]-carbamic acid benzyl ester
-
-
0.000041
[1-(1-[1-benzyl-4-[2-(2-benzyloxycarbonylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-5-phenyl-pentylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
-
-
additional information
additional information
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000128
(1-[1-[1-(4-[2-[2-(2-Benzyloxycarbonylamino-3-hydroxy-propionylamino)-propionylamino]-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butylcarbamoyl)-2-methyl-propylcarbamoyl]-ethylcarbamoyl]-2-hydroxy-ethyl)-carbamic acid benzyl ester
feline immunodeficiency virus
-
IC50: 128 nM
0.67
(3S,4R,5R,6S)-3,6-di-O-(3',5'-difluorobenzyl)-3,4,5,6-tetrahydroxyazepane
feline immunodeficiency virus
-
IC50: 0.67 mM
1.4
(3S,4R,5R,6S)-3,6-di-O-(3'-fluorobenzyl)-3,4,5,6-tetrahydroxyazepane
feline immunodeficiency virus
-
IC50: 1.4 mM
0.000138
2-(2-Benzenesulfonylamino-propionylamino)-N-[4-[2-(2-benzenesulfonylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butyl]-3-methyl-butyramide
feline immunodeficiency virus
-
IC50: 138 nM
0.000141
2-[2-(4-Bromo-benzenesulfonylamino)-propionylamino]-N-(4-[2-[2-(4-bromo-benzenesulfonylamino)-propionylamino]-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butyl)-3-methyl-butyramide
feline immunodeficiency virus
-
IC50: 141 nM
0.000212
2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-N-(4-[2-[2-acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-1-benzyl-2,3-dihydroxy-5-phenyl-pentyl)-3-methyl-butyramide
feline immunodeficiency virus
-
IC50: 212 nM
0.000048
3-(2-Hydroxy-3-[2-[2-(hydroxy-methyl-amino)-3-phenyl-propionylamino]-3-methyl-butyrylamino]-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
feline immunodeficiency virus
-
IC50: 48 nM
0.000117
3-(2-Hydroxy-3-[2-[2-(hydroxy-methyl-amino)-3-phenyl-propionylamino]-3-methyl-butyrylamino]-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (3-methyl-2-methylamino-butyryl)-amide
feline immunodeficiency virus
-
IC50: 117 nM
0.000182
3-(2-Hydroxy-3-[2-[2-(hydroxy-methyl-amino)-propionylamino]-3-methyl-butyrylamino]-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
feline immunodeficiency virus
-
IC50: 182 nM
0.000256
3-(3-[2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-2-hydroxy-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
feline immunodeficiency virus
-
IC50: 256 nM
0.00008
3-(3-[2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-2-hydroxy-4-phenyl-butyryl)-5,5-dimethyl-thiazolidine-4-carboxylic acid (3-methyl-2-methylamino-butyryl)-amide
feline immunodeficiency virus
-
IC50: 80 nM
0.0012
3-(3-[2-[2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino]-2-hydroxy-4-phenyl-butyryl)-thiazolidine-4-carboxylic acid (2-methoxyamino-3-methyl-butyryl)-amide
feline immunodeficiency virus
-
IC50: 0.0012 mM
0.0004
Gly-Ser-Gly-Val-Phe[CH2NH]-Val-Val-Asn-Gly-Leu
feline immunodeficiency virus
-
IC50: 0.0004 mM
0.005
Gly-Ser-Gly-Val-Phe[CHOHCH2]-Val-Val-Asn-Gly-Leu
feline immunodeficiency virus
-
IC50: 0.005 mM
0.00031
N-(2,3-Dihydroxy-4-[2-[2-(4-methoxy-benzenesulfonylamino)-propionylamino]-3-methyl-butyrylamino]-1,4-diphenyl-butyl)-2-[2-(4-methoxy-benzenesulfonylamino)-propionylamino]-3-methyl-butyramide
feline immunodeficiency virus
-
IC50: 310 nM
0.2
N-(2,3-Dihydroxy-4-[3-methyl-2-[2-(3-p-tolyl-ureido)-propionylamino]-butyrylamino]-1,4-diphenyl-butyl)-3-methyl-2-[2-(3-p-tolyl-ureido)-propionylamino]-butyramide
feline immunodeficiency virus
-
IC50: 0.2 mM
0.000017
N-(2,3-Dihydroxy-4-[3-methyl-2-[2-(toluene-4-sulfonylamino)-propionylamino]-butyrylamino]-1,4-diphenyl-butyl)-3-methyl-2-[2-(4-methyl-cyclohexa-1,3-dienesulfonylamino)-propionylamino]-butyramide
feline immunodeficiency virus
-
IC50: 17 nM
0.000228
N-(2,3-Dihydroxy-4-[3-methyl-2-[2-(toluene-4-sulfonylamino)-propionylamino]-butyrylamino]-1,4-diphenyl-butyl)-3-methyl-2-[2-(4-nitro-cyclohexa-1,3-dienesulfonylamino)-propionylamino]-butyramide
feline immunodeficiency virus
-
IC50: 228 nM
0.000156
N-[1-(1-[4-[2-(2-Benzoylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-benzamide
feline immunodeficiency virus
-
IC50: 156 nM
0.2
N-[2,3-Dihydroxy-4-(2-[2-[3-(4-methoxy-phenyl)-ureido]-propionylamino]-3-methyl-butyrylamino)-1,4-diphenyl-butyl]-2-[2-[3-(4-methoxy-phenyl)-ureido]-propionylamino]-3-methyl-butyramide
feline immunodeficiency virus
-
IC50: 0.2 mM
0.119
N-[2,3-Dihydroxy-4-(3-methyl-2-[2-[3-(4-trifluoromethoxy-phenyl)-ureido]-propionylamino]-butyrylamino)-1,4-diphenyl-butyl]-3-methyl-2-[2-[3-(4-trifluoromethoxy-phenyl)-ureido]-propionylamino]-butyramide
feline immunodeficiency virus
-
IC50: 0.119 mM
0.2
N-[2,3-Dihydroxy-4-(3-methyl-2-[2-[3-(4-trifluoromethyl-phenyl)-ureido]-propionylamino]-butyrylamino)-1,4-diphenyl-butyl]-3-methyl-2-[2-[3-(4-trifluoromethyl-phenyl)-ureido]-propionylamino]-butyramide
feline immunodeficiency virus
-
IC50: 0.2 mM
0.000118
N-[2,3-Dihydroxy-4-[3-methyl-2-(2-phenylmethanesulfonylamino-propionylamino)-butyrylamino]-1,4-diphenyl-butyl]-3-methyl-2-(2-phenylmethanesulfonylamino-propionylamino)-butyramide
feline immunodeficiency virus
-
IC50: 118 nM
0.0011
protease inhibitor AB-2
feline immunodeficiency virus
-
a HIV-1 protease inhibitor, IC50: 0.0011 mM
0.001
protease inhibitor AB-6
feline immunodeficiency virus
-
a HIV-1 protease inhibitor, IC50: 0.001 mM
0.008
protease inhibitor AB-8
feline immunodeficiency virus
-
a HIV-1 protease inhibitor, IC50: 0.008 mM
0.001
protease inhibitor APV-1
feline immunodeficiency virus
-
a HIV-1 protease inhibitor, IC50: 0.001 mM
0.045
protease inhibitor RTV
feline immunodeficiency virus
-
a HIV-1 protease inhibitor, weak inhibition of wild-type FIV protease, IC50: 0.045 mM
0.00009
protease inhibitor TL-3
feline immunodeficiency virus
-
IC50: 90 nM
0.0001
TL3
feline immunodeficiency virus
-
IC50: 100 nM
0.0002
[1-(1-[1-Benzyl-2,3,3-trihydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-propylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
feline immunodeficiency virus
-
IC50: 200 nM
0.001
[1-(1-[1-Benzyl-2-hydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-3-oxo-propylcarbamoyl]-2-methyl-propylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-carbamic acid benzyl ester
feline immunodeficiency virus
-
IC50: 0.001 mM
0.019
[1-(1-[1-Benzyl-2-hydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-3-oxo-propylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
feline immunodeficiency virus
-
IC50: 0.019 mM
0.0052
[1-(1-[1-Benzyl-2-hydroxy-3-[4-(2-methoxyamino-3-methyl-butyrylcarbamoyl)-5,5-dimethyl-thiazolidin-3-yl]-propylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
feline immunodeficiency virus
-
IC50: 0.0052 mM
0.0001
[1-(1-[4-[2-(2-Benzyloxycarbonylamino-propionylamino)-3-methyl-butyrylamino]-2,3-dihydroxy-1,4-diphenyl-butylcarbamoyl]-2-methyl-propylcarbamoyl)-ethyl]-carbamic acid benzyl ester
feline immunodeficiency virus
-
IC50: 100 nM
0.000095
[1-[1-(1-Benzyl-3-[4-[2-(2-benzyloxycarbonylamino-propionylamino)-3-methyl-butyrylcarbamoyl]-5,5-dimethyl-thiazolidin-3-yl]-2,3,3-trihydroxy-propylcarbamoyl)-2-methyl-propylcarbamoyl]-ethyl]-carbamic acid benzyl ester
feline immunodeficiency virus
-
IC50: 95 nM
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10790
-
matrix-assisted laser desorption ionization analysis
13300
ionization mass spectrometry
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
complex of the D30N mutant enzyme with the statine-based inhibitor LP-149 as well as with a substrate based on a modification of the inhibitor, LP-149S
crystal structure (1.7 A) of FIV protease is obtained in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12XFIV PR). The chimeric PR is crystallized in complex with inhibitor TL-3. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-type FIV PR reveal the information of additional van der Waals interactions between the enzyme inhibitor in the mutant PR
-
crystal structure determination and analysis, recombinant enzyme
-
hanging-drop vapor diffusion technique, crystals are grown at 4°C, crystal structure of the enzyme in complex with LP-130
-
mutant I37V/N55M/V59I/I98S/Q99V/P100N in complex with HIV inhibitors darunavir and lopinavir, to 1.7 and 1.8 A resolution, respectively. A flexible 90s loop and residue 98 play roles in supporting Gag processing and infectivity, residue 37 is involved in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Ile37Val preserves tertiary structure but prevents steric clashes with the inhibitors. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to darunavir. Ile98Pro-Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to the inhibitors, and Pro100Asn forms compensatory hydrogen bonds
structure of enzyme-inhibitor complex with LP-149
-
the two enzymes FIV protease and HIV-1 protease are strikingly similar at the crystallographic level, particularly within the substrate binding region
-
wild-type and mutant enzymes V59I and Q99V are cocrystallized with the C2-symmetric inhibitor TL-3, which contains (1S,2R,3R,4S)-1,4-diamino-1,4-dibenzyl-2,3-diol as the P1-P1' unit and Ala at P3/P3' positions
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
37°C, 0.2 M NaCl, wild-type enzyme loses 65% of ist activity
647835
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
pH 7.0, 0.2 M NaCl, wild-type enzyme loses 65% of its activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
during purification the recombinant enzyme underwent autoproteolysis to give discrete cleavage products. Construction of cleavage-resistant proteases which have Km and turnover-values similar to thoses of wild-type enzyme
-
recombinant enzyme from Escherichia coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli, unit-length enzyme with the addition of a Met and Ala at the N-terminus. This results in an enzyme with only an additional Ala on the N-terminus with respect to the wild-type enzyme. The N-terminal Met is removed during expression presumably by an Escherichia coli methionine amino peptidase
-
expression of wild-type and mutant FIV PRs in human 293T cells
-
mutant enzmyes V59I, Q99V and G5I/N55T/C84K, expression in Escherichia coli BL21 cells
-
the enzyme is encoded in the 5' end of the pol gene of FIV, nucleotide sequence determination, high-level recombinant expression, expression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G5I/N55T
-
only 25% loss of activity after 16 h at pH 7.0, 37°C, in 0.2 M NaCl, compared to 65% loss of the wild-type enzyme
G5I/N55T/C84K
-
autoproteolysis-resistant mutant, no significant change in Km or turnover number values between the mutant enzyme and the wild-type enzyme
I35D/I37V
-
mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I37V/L97T/I98P/Q99V/P100N/L101I
-
mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I37V/Q54K/N55M/M56I/I57G/V59I
-
mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I37V/Q54K/N55M/M56I/I57G/V59I/L97T/I98P/Q99V/
-
mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I57G
-
mutant enzyme shows no activity against either FIV or HIV substrates
I35D/M56I
-
mutant enzyme shows no activity against either FIV or HIV substrates
I35D/Q54K
-
mutant enzyme shows no activity against either FIV or HIV substrates
I35D/V59I
-
mutant enzyme shows no activity against either FIV or HIV substrates
I37V/N55M/M56I/I57G/V59I/G62F/K63I/L97T/I98P/Q99V/P100N/L101I
-
crystal structure (1.7 A) of FIV protease is obtained in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12XFIV PR). The chimeric PR is crystallized in complex with inhibitor TL-3. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-type FIV PR reveal the information of additional van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retains the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR
I37V/N55M/V59I/I98P/Q99V/P100N
-
the mutant shows low-level infectivity ex vivo, and after passage, progeny that exhibits a higher growth rate emerged. The mutant enzyme is sensitive to the HIV-1 PR inhibitors lopinavir and darunavir, as well as to the broad-based inhibitor TL-3
I37V/N55M/V59I/I98S/Q99V/P100N
chimeric feline immunodeficiency virus protease that supports infectivity but confers sensitivity to the human immunodeficiency virus protease inhibitors darunavir and lopinavir. The protease has five replacements mimicking homologous residues in HIV protease and a sixth which mutated from Pro to Ser during selection
L101I
-
mutant enzyme with dramatically reduced activity
L97T
-
in addition to poor/delayed cleavage at the FIV NC-p2 junction, inefficient processing at the FIV matrix-capsid cleavage junction by the L97T mutant is also observed
N55D
-
site-directed mutagenesis, the mutant shows similar activity compared to the wild-type enzyme
N55T
-
only 25% loss of activity after 16 h at pH 7.0, 37°C, in 0.2 M NaCl, compared to 65% loss of the wild-type enzyme
P100N
-
the mutant shows low-level infectivity
Q64K
-
mutant enzyme with dramatically reduced activity
D30N
-
inactive mutant; site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
-
I35D
-
site-directed mutagenesis, the mutant shows about 30% reduced activity compared to the wild-type enzyme
-
I57G
-
site-directed mutagenesis, the mutant shows about 50% reduced activity compared to the wild-type enzyme
-
N55D
-
site-directed mutagenesis, the mutant shows similar activity compared to the wild-type enzyme
-
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
-
PR is an important target for antiviral therapies since PR is reponsible for the processing of viral Gag and Gag-Pol polyproteins into individual structural and enzymatic proteins during assembly and maturation. This proteolytic step is highly specific, ordered and essential for producing mature and infectious retrovirus particles
molecular biology