Information on EC 3.4.23.47 - HIV-2 retropepsin

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The expected taxonomic range for this enzyme is: Human immunodeficiency virus 2

EC NUMBER
COMMENTARY hide
3.4.23.47
-
RECOMMENDED NAME
GeneOntology No.
HIV-2 retropepsin
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Endopeptidase for which the P1 residue is preferably hydrophobic
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
144114-21-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ac-Tyr-Arg-Ala-Arg-Val-Phe Nph-Val-Arg-Ala-Ala-Lys + H2O
Ac-Tyr-Arg-Ala-Arg-Val-Phe + Nph-Va-Arg-Ala-Ala-Lys
show the reaction diagram
-
chromogenic substrate
-
-
?
CTLNF + PISP + H2O
CTLNF + PISP
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in PR/RT
-
-
?
DKELYPLTSL + H2O
DKELY + PLTSL
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in p6
-
-
?
EKGGNY PVQHV + H2O
?
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in MA/CA
-
-
?
GAG precursor protein F16 of HIV-1 + H2O
?
show the reaction diagram
GAG precursor protein of HIV-2 + H2O
?
show the reaction diagram
HIV-1 Gag-Pol poylprotein + H2O
?
show the reaction diagram
-
site-specific proteolytic cleavage, protein precursors and peptides derived thereof
-
-
?
HIV-2 Gag-Pol poylprotein + H2O
?
show the reaction diagram
-
site-specific proteolytic cleavage, protein precursors and peptides derived thereof
-
-
?
IPFAA AQQRK + H2O
?
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in X/NC
-
-
?
IPFAAAQQRK + H2O
IPFAA + AQQRK
show the reaction diagram
-
peptide represents the HIV-2 cleavage site p2/NC
-
-
?
IRKILFLDG + H2O
IRKIL + FLDG
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in RT/IN
-
-
?
KARLMAEALK + H2O
KARLM + AEALK
show the reaction diagram
KARVLAEAMS + H2O
KARVL + AEAMS
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage CA/X
-
-
?
KPRNFPVAQV + H2O
KPRNF + PVAQV
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in NC/p6
-
-
?
Lys-Ala-Arg-Ile-Nle Nph-Glu-Ala-Nle-NH2 + H2O
Lys-Ala-Arg-Ile-Nle + Nph-Glu-Ala-Nle-NH2
show the reaction diagram
-
chromogenic substrate
-
-
?
Lys-Ala-Arg-Val-Nle-(4-nitrophenylalanine)-Glu-Ala-Nle + H2O
?
show the reaction diagram
-
-
-
-
?
Lys-Ala-Arg-Val-Nle-Nph-Glu-Ala-Nle-NH2 + H2O
Lys-Ala-Arg-Val-Nle + Nph-Glu-Ala-Nle-NH2
show the reaction diagram
-
the enzyme is highly active with peptide substrates containing variations of this cleavage sequence
-
-
?
Lys-Ala-Arg-Val-Nle-p-nitrophenylalanine-Glu-Ala-Nle-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
MSLNL PVAKV + H2O
?
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in TF/PR
-
-
?
myristylated p53-Gag precursor + H2O
?
show the reaction diagram
-
-
-
-
?
NH2-ATLNFPSPW-COOH + H2O
?
show the reaction diagram
-
-
-
-
?
p24-Gag protein + H2O
?
show the reaction diagram
-
-
-
-
?
poly(A)-binding protein 1 + H2O
?
show the reaction diagram
-
it is shown that HIV-1 and HIV-2 protease cleaves poly(A)-binding protein 1 directly at positions 237 and 477, separating the two first RNA-recognition motifs from the C-terminal domain of poly(A)-binding protein and additional cleavage site at position 410 is detected for HIV2-protease
-
-
-
RGLAAPQFSL + H2O
RGLAA + PQFS
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage in TF/PR
-
-
?
RPQNFLQSRP + H2O
?
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage NC/p6
-
-
?
TATIMMQRGN + H2O
TATIM + MQRGN
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage X/NC
-
-
?
Val-Ser-Gln-Ala-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Ala-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Asn-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Cys-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Cys-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Gly-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Gly-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Ile-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Ile-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Leu-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Leu-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Phe-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Phe-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Thr-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Thr-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
Val-Ser-Gln-Val-Tyr-Pro-Ile-Val-Gln + H2O
Val-Ser-Gln-Val-Tyr + Pro-Ile-Val-Gln
show the reaction diagram
-
-
-
?
VLQNYPIVQ + H2O
VLQNY + PIVQ
show the reaction diagram
VSQLYPIVQ + H2O
VSQLY + PIVQ
show the reaction diagram
VSQNYPIVQ + H2O
?
show the reaction diagram
-
oligopeptide representing cleavage sites in HIV-1 Gag and Gag-Pol polyproteins, location of cleavage MA/CA
-
-
?
VSQNYPIVQ + H2O
VSQNY + PIVQ
show the reaction diagram
-
oligopeptide substrate
-
-
?
VSQNYPLVQ + H2O
VSQNY + PLVQ
show the reaction diagram
-
oligopeptide substrate
-
-
?
VSQVYPIVQ + H2O
VSQVY + PIVQ
show the reaction diagram
-
peptide represents a variation of HIV-1 MA/CA cleavage site
-
-
?
VVQNYPIVQ + H2O
VVQNY + PIVQ
show the reaction diagram
-
peptide represents a variation of HIV-1 MA/CA cleavage site
-
-
?
YVSQNFPIVQNR + H2O
YVSQNF + PIVQNR
show the reaction diagram
-
synthetic peptide substrate based on the Ma/Ca cleavage site of HIV-1 Gag
-
-
?
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 precursor protein of HIV-2 + H2O
?
show the reaction diagram
additional information
?
-
-
enzyme undergoes autoproteolysis at pH 3 at the G35/I36 site
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R,4S,5S)-6-cyclohexyl-5-(3,3-dimethylbutanamido)-4-hydroxy-2-isopropyl-N-((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)hexanamide
-
synthetic inhibitor 4
(hydroxyethyl)amide isostere
-
-
-
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(4,6-dimethylpyrimidin-2-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
-
hydroxyethylamine dipeptide isostere inhibitor 3
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylmethoxy)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
-
hydroxyethylamine dipeptide isostere inhibitor 5
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
-
hydroxyethylamine dipeptide isostere inhibitor 2
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-4-ylsulfonyl)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
-
hydroxyethylamine dipeptide isostere inhibitor 4
2,6-dimethylbenzyl (2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-4-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylcarbamate
-
hydroxyethylamine dipeptide isostere inhibitor 1
acetyl-pepstatin
amprenavir
benzyl (S)-1-((2S,3R)-4-((R)-4-(tert-butylcarbamoyl)thiazolidin-3-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-ylcarbamate
-
synthetic inhibitor 1
benzyl (S)-1-((2S,3R)-4-((S) -2-(tert-butylcarbamoyl)indolin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-ylcarbamate
-
synthetic inhibitor 2
BI-LA-398-Phe-Val-Phe-psi-Ch2NH-Leu-Glu-Ile-amide
-
-
-
darunavir
H-261
-
renin inhibitor
H2O2
-
inactivated after oxidation at the dimer interface, activity can be partly restored with methionine sulphoxide reductase
indinavir
lopinavir
monoclonal antibody 1696
-
-
-
N-((S)-1-((2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylmethoxy)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-3-methyl-1-oxobutan-2-yl)quinoline-2-carboxamide
-
hydroxyethylamine dipeptide isostere inhibitor 8
N-((S)-1-((2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylmethylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-3-methyl-1-oxobutan-2-yl)quinoline-2-carboxamide
-
hydroxyethylamine dipeptide isostere inhibitor 6
N-((S)-1-((2S,3R)-4-((2S,4R)-2-(tert-butylcarbamoyl)-4-(pyridin-3-ylthio)piperidin-1-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-3-methyl-1-oxobutan-2-yl)quinoline-2-carboxamide
-
hydroxyethylamine dipeptide isostere inhibitor 7
N-((S)-1-((2S,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl)-octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-yl)quinoline-3-carboxamide
-
synthetic inhibitor 3
psi-ix VSFNF(psi)PQITL
-
competitive inhibition
-
psi-x CTLNF(psi)PISP
-
competitive inhibition
-
tert-butyl (2S,3S)-5-(((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)carbamoyl)-1-cyclohexyl-3-hydroxy-6-methylheptan-2-ylcarbamate
-
synthetic inhibitor 6
tert-butyl (2S,3S,5R)-5-(((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)carbamoyl)-1-cyclohexyl-3-hydroxy-6-methylheptan-2-ylcarbamate
-
synthetic inhibitor 5
additional information
-
no inhibition with 1,10-phenanthroline and phenylmethylsulfonylfluoride or EDTA
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.36
Ac-Tyr-Arg-Ala-Arg-Val-Phe Nph-Val-Arg-Ala-Ala-Lys
-
pH 4.7, 37°C
-
0.06
CTLNFPISP
-
pH 5.6, 37°C
0.42
DKELYPLTSL
-
pH 5.6, 37°C
0.07
IPFAA AQQRK
-
pH 5.6, 37°C
0.28
IPFAAAQQRK
-
pH 5.6, 37°C
0.005
IRKILFLDG
-
pH 5.6, 37°C
0.08
KARLM AEALK
-
pH 5.6, 37°C
0.13
KARLMAEALK
-
pH 5.6, 37°C
0.03
KARVL-AEAMS
-
pH 5.6, 37°C
0.08
L-threonyl-L-alanyl-L-threonyl-L-isoleucyl-L-methionyl-L-methionyl-L-glutaminyl-L-arginylglycyl-L-asparagine
-
pH 5.6, 37°C
0.025
Lys-Ala-Arg-Ile-Nle Nph-Glu-Ala-Nle-NH2
-
pH 4.7, 37°C
0.071 - 0.072
Lys-Ala-Arg-Val-Nle-(4-nitrophenylalanine)-Glu-Ala-Nle
0.05
Lys-Ala-Arg-Val-Nle-p-nitrophenylalanine-Glu-Ala-Nle-NH2
-
-
0.02
MSLNL PVAKV
-
pH 5.6, 37°C
-
0.74 - 0.95
NH2-ATLNFPSPW-COOH
0.07
RGLAAPQFSL
-
pH 5.6, 37°C
0.3
RPQNFLQSRP
-
pH 5.6, 37°C
-
0.099 - 0.4
VLQNYPIVQ
0.12 - 0.203
VSQLYPIVQ
0.172 - 0.18
VSQNYPIVQ
0.223
VSQNYPLVQ
-
pH 5.6, 37°C
0.24
VSQVYPIVQ
-
pH 5.6, 37°C
0.19
VVQNYPIVQ
-
pH 5.6, 37°C
0.16
YVSQNFPIVQNR
-
pH 4.7
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00167
Ac-Tyr-Arg-Ala-Arg-Val-Phe Nph-Val-Arg-Ala-Ala-Lys
Human immunodeficiency virus 2
-
pH 4.7, 37°C
-
0.000267 - 0.00283
AETF YVDGAA
-
0.0001
CTLNFPISP
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.000025
DKELYPLTSL
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.00055 - 0.00917
EKGGNY PVQHV
-
0.000217
IPFAA AQQRK
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.3
IPFAAAQQRK
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.000333
IRKILFLDG
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.000333
KARLM AEALK
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.3
KARLMAEALK
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.00025
KARVL-AEAMS
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.000183 - 0.0117
KPRNFPVAQV
0.000967
L-threonyl-L-alanyl-L-threonyl-L-isoleucyl-L-methionyl-L-methionyl-L-glutaminyl-L-arginylglycyl-L-asparagine
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.00722
Lys-Ala-Arg-Ile-Nle Nph-Glu-Ala-Nle-NH2
Human immunodeficiency virus 2
-
pH 4.7, 37°C
5.6 - 6.4
Lys-Ala-Arg-Val-Nle-(4-nitrophenylalanine)-Glu-Ala-Nle
5.3
Lys-Ala-Arg-Val-Nle-p-nitrophenylalanine-Glu-Ala-Nle-NH2
Human immunodeficiency virus 2
-
-
0.000333
MSLNL PVAKV
Human immunodeficiency virus 2
-
pH 5.6, 37°C
-
3 - 4.33
NH2-ATLNFPSPW-COOH
0.000717
RGLAAPQFSL
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.00005
RPQNFLQSRP
Human immunodeficiency virus 2
-
pH 5.6, 37°C
-
0.0000333 - 0.06
VLQNYPIVQ
0.0011 - 0.4
VSQLYPIVQ
0.00172 - 0.00213
VSQNYPIVQ
0.00303
VSQNYPLVQ
Human immunodeficiency virus 2
-
pH 5.6, 37°C
2.6
VSQVYPIVQ
Human immunodeficiency virus 2
-
pH 5.6, 37°C
0.16
VVQNYPIVQ
Human immunodeficiency virus 2
-
pH 5.6, 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.1
IPFAAAQQRK
Human immunodeficiency virus 2
-
pH 5.6, 37°C
11712
2.3
KARLMAEALK
Human immunodeficiency virus 2
-
pH 5.6, 37°C
12196
0.2
VLQNYPIVQ
Human immunodeficiency virus 2
-
pH 5.6, 37°C
5743
3.3
VSQLYPIVQ
Human immunodeficiency virus 2
-
pH 5.6, 37°C
4965
10.8
VSQVYPIVQ
Human immunodeficiency virus 2
-
pH 5.6, 37°C
5753
0.8
VVQNYPIVQ
Human immunodeficiency virus 2
-
pH 5.6, 37°C
6804
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0007
(2R,4S,5S)-6-cyclohexyl-5-(3,3-dimethylbutanamido)-4-hydroxy-2-isopropyl-N-((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)hexanamide
-
pH 4.7, 37°C, synthetic inhibitor 4
0.0000012
(hydroxyetyhl)amide isostere
-
-
-
0.000005
acetyl-pepstatin
-
pH 4.7, competitive versus YVSQNFPIVQNR
0.0000044 - 0.17
amprenavir
0.0000024
atazanavir
-
-
0.0002
benzyl (S)-1-((2S,3R)-4-((R)-4-(tert-butylcarbamoyl)thiazolidin-3-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-ylcarbamate
-
pH 4.7, 37°C, synthetic inhibitor 1
0.00000017 - 0.04
darunavir
0.0000013
indinavir
-
-
0.0000014
KNI-764
-
-
0.0000007
lopinavir
-
-
0.0002
N-((S)-1-((2S,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl)-octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-phenylbutan-2-ylamino)-4-amino-1,4-dioxobutan-2-yl)quinoline-3-carboxamide
-
pH 4.7, 37°C, synthetic inhibitor 3
0.0000027
nelfinavir
-
-
0.000015
pepstatin A
-
pH 4.7
0.000025
psi-ix VSFNF(psi)PQITL
-
pH 5.6, 37°C
-
0.0006
psi-x CTLNF(psi)PISP
-
pH 5.6, 37°C
-
0.0000008
ritonavir
-
-
0.0000006 - 0.11
saquinavir
0.0004
tert-butyl (2S,3S,5R)-5-(((2S,3R)-3-methyl-1-oxo-1-(phenethylamino)pentan-2-yl)carbamoyl)-1-cyclohexyl-3-hydroxy-6-methylheptan-2-ylcarbamate
-
pH 4.7, 37°C, synthetic inhibitor 5
0.00000045
tipranavir
-
-
0.00000016
TMC-126
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000098 - 1
amprenavir
0.000016 - 0.001112
indinavir
0.000004 - 0.0166
lopinavir
0.000064 - 0.002564
nelfinavir
0.1472 - 0.554
saquinavir
0.000145 - 0.004436
tipranavir
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3
-
enzyme undergoes autoproteolysis at pH 3 at the G35/I36 site
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Human immunodeficiency virus type 2 subtype A
Human immunodeficiency virus type 2 subtype A
Human immunodeficiency virus type 2 subtype A
Human immunodeficiency virus type 2 subtype A
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22000
-
2 * 22000, Western blotting
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
self-processing of the immature progeny virus at the host cell membrane prior to virus budding, dimerization occurs before proteolytic cleavage
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulations in complerx with inhibitors amprenvir and darunavir
crystallized by hanging drop method in complex with a reduced amide inhibitor, BI-LA-398
-
crystallized by hanging drop method in complex with a reduced amide inhibitor, BI-LA-398; crystals grown by hanging-drop vapor diffusion method, thin tetragonal prisms, space group P4(1)2(1)2 or P4(3)2(1)2 with a=b=62.6 A and c=115.8 A
-
crystallized by hanging drop method in complex with a reduced amide inhibitor, BI-LA-398; monoclinic crystals, vapor diffusion, hanging drops, P2(1) space group with a =36.76 A, b=58.44 A, c= 55.11 A and beta=91.20°
-
crystallized by hanging drop method in complex with a reduced amide inhibitor, BI-LA-398; Phe-Val-Phe-psi-CH2NH-Leu-Glu-Ile-amide, space group P4(1) or P4(3), unit-cell parameters a=b=55.1 A, c=138.9 A
-
in complex with inhibitor amprenavir, to 1.5 A resolution, and comparison with HIV-1 protease PR1M
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substrate binding pocket structure analysis
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
Tm: 60.5°C, binding of darunavir increases Tm by 14.8°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activity is lost during purification and storage
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivated after oxidation at the dimer interface, activity can be partly restored with methionine sulphoxide reductase
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644068, 644069
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, stored in 10 mM potassium phosphate, pH 7.5, containing 125 mM KCl and 0.0125% Tween 20
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4°C, phosphate buffer pH 6 and 50 mM NaCl, 72 h, no loss of activity
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stored at -20°C without loss of activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
mutant K7Q, autoproteolysis; recombinant enzyme
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product of synthetic gene
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purification of chemically synthesized enzyme
recombinant enzyme
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using anion-exchange Q-Sepharose column
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
BHK-21 (baby hamster kidney) cells and COS-7 cells are transfected with HIV-1 and HIV-2 protease and human poly(A)-binding protein 1
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cloned and expressed in Escherichia coli BL21
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cloned and expressed in Escherichia coli BL21(DE3)
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cloned and expressed in Escherichia coli JM-101, F' and X90
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cloned and sequenced
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expressed in Escherichia coli
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genes constructed encode HIV-2 homodimeric and heterodimeric proteinases, expression in Escherichia coli K-12 strain MC1061
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genetic organization, processing steps, expression of the viral enzyme in bacterial and yeast recombinant systems
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HIV-2 protease is expressed in yeast cells
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synthetic gene for HIV-2 protease constructed and expressed in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D25N
-
inactive mutant forms a dimer
DELTA96-99
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dimer interface mutations such as a deletion of the C-terminal residues 96-99 (PR21-95), drastically increase the Kd. Deletion mutant consists predominantly of folded monomers. Addition of 2fold excess active-site inhibitor does not promote dimerization
E37K
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mutation significantly retards autoproteolytic cleavage during expression. Mutant shows a higher dimer dissociation constant, Kd, compared to wild-type. Km and kcat values for substrate Lys-Ala-Arg-Val-Nle-(4-nitrophenylalanine)-Glu-Ala-Nle comparable to wild-type
I50V
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IC50 (mM): value above 10 (amprenavir), 0.000072 (idinavir), 0.000132 (nelfinavir), 0.000316 (tipranavir), 0.000203 (lopinavir)
I54M/I84V
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IC50 (mM): value above 10 (amprenavir), 0.000388 (idinavir), 0.001747 (nelfinavir), 0.002028 (tipranavir), 0.000375 (lopinavir)
I54M/L90M
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IC50 (mM): value above 10 (amprenavir), 0.001112 (idinavir), 0.002564 (nelfinavir), 0.000145 (tipranavir), 0.000524 (lopinavir)
I54M/L99F
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IC50 (mM): value above 10 (amprenavir), 0.000825 (idinavir), 0.002241 (nelfinavir), 0.002908 (tipranavir), 0.000414 (lopinavir)
I82F
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IC50 (mM): 0.000965 (amprenavir), 0.000544 (idinavir), 0.000244 (nelfinavir), 0.000306 (tipranavir), 0.000145 (lopinavir)
I82L
-
IC50 (mM): 0.000528 (amprenavir), 0.000064 (idinavir), 0.000106 (nelfinavir), 0.00016 (tipranavir), 0.000075 (lopinavir)
I82L/L99F
-
IC50 (mM): 0.000098 (amprenavir), 0.000143 (idinavir), 0.000961 (nelfinavir), 0.000524 (tipranavir), 0.000496 (lopinavir)
K45R
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mutant is resistant toward HIV-2 protease inhibitor lopinavir and saquinavir in yeast
L90M
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IC50: 0.0125 (lopinavir), 0.554 (saquinavir), L90M mutation present in primary HIV-2 isolate, modifies the HIV-2 protease susceptibility to saquinavir but not lopinavir
L99F
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IC50: 0.0111 (lopinavir), 0.1472 (saquinavir)
M76V
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mutant is resistant toward HIV-2 protease inhibitor lopinavir and saquinavir in yeast
T26A
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dimer interface mutations in the active site of PR2 drastically increase the Kd. T26A consists predominantly of folded monomers. Addition of 2fold excess active-site inhibitor promotes dimerization of mutant PR2T26A
V47A/D17N
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passage of HIV-2MS with increasing concentrations of lopinavir selects mutations V47A and D17N in the HIV-2 protease gene. Introduction of both 17N and 47A either individually or together into HIV-2ROD molecular infectious clones shows that the single V47A substitution in HIV-2 results in a substantial reduction in susceptibility to lopinavir. This mutant retains wild-type susceptibility to other proteinase inhibitors and is hypersusceptible to atazanavir and saquinavir
V71I, L90M, I89V
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most frequently detected mutations within PR selected under antiretroviral drug therapy in a clinical cohort study with 25 patients treated with antiretroviral therapy
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
renaturation of purified chemically synthesized enzyme
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
molecular biology
-
an experimental model system based on the expression of HIV-2 protease in yeast cells is established: HIV-2 protease activity kills the yeast cell, this process can be abolished by inhibiting the viral enzyme activity