Information on EC 3.4.23.50 - human endogenous retrovirus K endopeptidase

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The expected taxonomic range for this enzyme is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.4.23.50
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RECOMMENDED NAME
GeneOntology No.
human endogenous retrovirus K endopeptidase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Processing at the authentic HIV-1 PR recognition site and release of the mature p17 matrix and the p24 capsid protein, as a result of the cleavage of the -SQNY-/-PIVQ- cleavage site.
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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-
-
-
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
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala + H2O
?
show the reaction diagram
-
-
-
-
?
2-aminobenzoyl-ATHQVY-(4-nitro)FVRKA + H2O
2-aminobenzoyl-ATHQVY + (4-nitro)FVRKA
show the reaction diagram
-
-
-
-
?
Gag polyprotein + H2O
?
show the reaction diagram
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the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
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-
?
Gag-Pol polyprotein + H2O
?
show the reaction diagram
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the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
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-
?
HERV-K Gag polyprotein + H2O
?
show the reaction diagram
HIV-1 matrix-capsid polyprotein + H2O
?
show the reaction diagram
KARVY-(4-nitro)FEA-Nle-NH2 + H2O
KARVY + (4-nitro)FEA-Nle-NH2
show the reaction diagram
-
-
-
-
?
Lys-Ala-Arg-Val-Tyr-Phe(NO2)-Glu-Ala-Nle-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
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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 polyprotein + H2O
?
show the reaction diagram
-
the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
-
-
?
Gag-Pol polyprotein + H2O
?
show the reaction diagram
-
the enzyme is synthesized as part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature dimer
-
-
?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NaCl
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1 M, activates
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ABT538
-
-
indinavir
KNI227
-
-
KNI272
-
-
L735,524
-
-
Pepstatin
pepstatin A
Q8467
-
-
ritonavir
Ro31-8624
-
-
Ro31-8959
-
-
saquinavir
SD145
-
-
SD146
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; efficiently blocks HERV-K Gag processing in vitro and in cells
SD152
-
-
XK234
-
-
XM412
-
-
XV638
-
-
XV643
-
-
XV644
-
-
XV648
-
-
XV651
-
-
XV652
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-
XW805
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-
additional information
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the enzyme is highly resistant to all the HIV-1 PR inhibitors tested, including L-735,524, Ro31-8959, and ABT 538
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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high ionic strength activates the enzyme
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 0.041
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala
0.001 - 0.0103
Lys-Ala-Arg-Val-Tyr-Phe(NO2)-Glu-Ala-Nle-NH2
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.13 - 1.37
2-aminobenzoyl-Ala-Thr-His-Gln-Val-Tyr-Phe(NO2)-Val-Arg-Lys-Ala
0.8 - 2.1
Lys-Ala-Arg-Val-Tyr-Phe(NO2)-Glu-Ala-Nle-NH2
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00006
ABT538
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pH 4.5, 11600 Da core domain
0.00061 - 0.00094
indinavir
0.0000046 - 0.000015
KNI227
0.00012 - 0.00034
KNI272
0.00257 - 0.0049
Pepstatin
0.0000162 - 0.000061
Q8467
0.00113 - 0.00121
ritonavir
0.00258 - 0.00574
saquinavir
0.0000059 - 0.00003
SD145
0.00000015 - 0.0000043
SD146
0.0000079 - 0.000027
SD152
0.00067 - 0.00187
XK234
0.000091 - 0.00039
XM412
0.0000022 - 0.00002
XV638
0.00000017 - 0.0000039
XV643
0.00000022 - 0.0000029
XV644
0.0000001 - 0.0000023
XV648
0.0000032 - 0.000043
XV651
0.00000052 - 0.0000033
XV652
0.0000036 - 0.000031
XW805
additional information
additional information
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-
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 5
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11600 Da core domain
4.5
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C-terminally truncated mutant enzyme, substrate KARVYF-NO2-EA-Nle-NH2
PDB
SCOP
CATH
ORGANISM
UNIPROT
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
16470
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avarage molecular weight under near physiological conditions, sedimentation equilibrium analysis
17500
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2 * 17500, the enzyme is synthesized as monomeric part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature protein dimer, structure overview
43000
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SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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2 * 17500, the enzyme is synthesized as monomeric part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature protein dimer, structure overview
additional information
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the 11600 Da core domain exists as a dimer at pH 7.0
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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the enzyme is synthesized as monomeric part of the Gag polyprotein or the Gag-Pol polyprotein and autolytically processed to the mature protein dimer, autoprocessing at the N-terminal sequence Lys-Ala-Ala-Tyr-Trp-Ala-Ser-Gln
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3 - 9
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room temperature, prolonged incubation, 60% remaining activity in presence or absence of 1 M NaCl, no autolysis
668800
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
18200 Da enzyme form and 11600 Da core domain
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full-length and C-terminally truncated enzyme in Escherichia coli
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recombinant wild-type and C-terminally truncated mutant enzymes from Escherichia coli by ammonium sulfate fractionation, cation and anion exchange chromatography, and hydrophobic interaction chromatography, or recombinant C-terminally truncated mutant enzyme from inclusion bodies by dialysis and pepstatin A affinity chromatography followed by autoprocession to active, soluble enzme
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
213 amino acids of the 3'-end of the HERV-K protease open reading frame are expressed in Escherichia coli. Autocatalytic cleavage of the expressed polypeptide results in a catalytically active 18200 Da protein
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expression of a full-length and C-terminally truncated enzyme in Escherichia coli
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nucleotide sequence determination and analysis, detailed phylogenetic analysis of virus from primates and humans, and structural analysis of 100 HERV-K(HML-5) provirus sequences, reconstruction of a coding-competent HML-5 provirus, overview
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sequence determination and analysis, expression of wild-type and C-terminally truncated mutant enzymes in Escherichia coli
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targeting of the HERV-K PR to protease-deficient HIV-1 virions by expressing it as a Vpr fusion partner. The Vpr fusion proteins are sucessfully delivered to the HIV-1 virions, where the HERV-K PR not only autoprocesses itself to ist mature form, but also cleaves a number of HIV-1 polyproteins
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the enzyme is expressed either as a full-length native protein or as truncated protein in Escherichia coli
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the HERV-K113 sequence is cloned into a small plasmid vector. It is shown that based on a substantial LTR-promoter activity, full length messenger RNA and spliced env-, rec- and 1.5 kb (hel)-transcripts are produced. Envelope protein of HERV-K113 is synthesized as an 85 kDa precursor that is found partially processed. The accessory Rec protein is highly expressed and accumulates in the nucleus. Expression analysis reveals synthesis of the Gag precursor and the protease in lysates of transfected HEK-293T cells. The cloned HERV-K113 provirus is not replication competent
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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a C-terminally truncated mutant enzyme shows increased affinity for the peptide substrates and increased sensitivity to peptidomimetic inhibitors compared to the wild-type enzyme
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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in the present study HIV-1 and HCV-1-positive plasma samples are screened for the presence of HERV-K(HML-2) RNA in an RT-PCR using HERV-K pol specific primers. Type 1 and type 2 HERV-K(HML- 2) viral RNA genomes are found to coexist in the same plasma of HIV-1 patients suggesting that HERV-K(HML-2) viral particles are induced in HIV-1-infected individuals