3.4.23.B4: Feline immunodeficiency virus protease
This is an abbreviated version!
For detailed information about Feline immunodeficiency virus protease, go to the full flat file.
Word Map on EC 3.4.23.B4
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3.4.23.B4
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broad-based
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polyproteins
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retroviral
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drug-resistant
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gag-pol
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flap
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subsites
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val
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calicivirus
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lopinavir
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lentivirus
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virions
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medicine
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molecular biology
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drug development
- 3.4.23.B4
-
broad-based
- polyproteins
-
retroviral
-
drug-resistant
- gag-pol
- flap
-
subsites
- val
- calicivirus
- lopinavir
- lentivirus
- virions
- medicine
- molecular biology
- drug development
Reaction
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 =
Synonyms
FCV protease, feline immunodeficiency virus protease, Feline immunodeficiency virus retropepsin, FIV PR, FIV protease, FIV retropepsin, FIV-PR, More
ECTree
3.4.23.B4 Feline immunodeficiency virus proteaseAdvanced search results
results (
results (Engineering
Engineering on EC 3.4.23.B4 - Feline immunodeficiency virus protease
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D30N
G5I/N55T
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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
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autoproteolysis-resistant mutant, no significant change in Km or turnover number values between the mutant enzyme and the wild-type enzyme
I35D
I35D/I37V
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I37V/L97T/I98P/Q99V/P100N/L101I
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I37V/Q54K/N55M/M56I/I57G/V59I
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I37V/Q54K/N55M/M56I/I57G/V59I/L97T/I98P/Q99V/
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D/I57G
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D/M56I
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D/Q54K
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D/V59I
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mutant enzyme shows no activity against either FIV or HIV substrates
I37V
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
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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
I57G
I98P
L97T
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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
M56I
N55D
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site-directed mutagenesis, the mutant shows similar activity compared to the wild-type enzyme
N55M
N55T
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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
Q99V
V59I
D30N
I35D
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site-directed mutagenesis, the mutant shows about 30% reduced activity compared to the wild-type enzyme
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I57G
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site-directed mutagenesis, the mutant shows about 50% reduced activity compared to the wild-type enzyme
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N55D
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site-directed mutagenesis, the mutant shows similar activity compared to the wild-type enzyme
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additional information
D30N
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site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
I35D
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mutant enzyme shows no activity against either FIV or HIV substrates
I35D
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site-directed mutagenesis, the mutant shows about 30% reduced activity compared to the wild-type enzyme
I37V
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mutant enzyme with full activity. Significant increase in activity against the HIV-I reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type enzyme. Increase in activity against two rapidly cleaved peptides selected by cleavage of phage display library with HIV-I protease. Mutant enzyme compared with wild-type enzyme shows inhibitor specificity more similar to that of the HIV-1 protease
I57G
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mutant enzyme shows no activity against either FIV or HIV substrates
I57G
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site-directed mutagenesis, the mutant shows about 50% reduced activity compared to the wild-type enzyme
M56I
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mutant enzyme with full activity. Mutant enzyme compared with wild-type enzyme shows inhibitor specificity more similar to that of the HIV-1 protease
N55M
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mutant enzyme with full activity. Significant increase in activity against the HIV-I reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type enzyme. Mutant enzyme compared with wild-type enzyme shows inhibitor specificity more similar to that of the HIV-1 protease
N55M
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the mutant gives processing patterns essentially identical to that of wild type enzyme
Q99V
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mutant enzyme shows decreased inhibition constant with C2-symmetric inhibitor TL-3 compared to wild-type enzyme
Q99V
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mutant enzyme with full activit. Significant increase in activity against the HIV-I reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type enzyme. Increase in activity against two rapidly cleaved peptides selected by cleavage of phage display library with HIV-I protease. Mutant enzyme compared with wild-type enzyme shows inhibitor specificity more similar to that of the HIV-1 protease
V59I
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mutant enzyme shows decreased inhibition constant with C2-symmetric inhibitor TL-3 compared to wild-type enzyme
V59I
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mutant enzyme with full activity. Significant increase in activity against the HIV-I reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type enzym. Increase in activity against two rapidly cleaved peptides selected by cleavage of phage display library with HIV-I protease. Mutant enzyme compared with wild-type enzyme shows inhibitor specificity more similar to that of the HIV-1 protease
V59I
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the mutant gives processing patterns essentially identical to that of wild type enzyme
D30N
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site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme
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additional information
multiple-substitution mutants are constructed by replacing the residues in and around the active site of the enzyme with structurally equivalent residues of HIV-1 protease. The findings indicate that maintainance of both substrate and inhibitor specificity as a function of interactions between residues both inside and outside the active site
additional information
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multiple-substitution mutants are constructed by replacing the residues in and around the active site of the enzyme with structurally equivalent residues of HIV-1 protease. The findings indicate that maintainance of both substrate and inhibitor specificity as a function of interactions between residues both inside and outside the active site
additional information
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construction of cleavage-resistant mutants which have Km-values and turnover numbers similar to those of the wild-type enzyme
additional information
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generation of autolysis defective mutant enzymes
additional information
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generation of different FIV PR mutants, by single point mutations and exchange of several amino acids comprising fragments, which show altered substrate specificity to Gag-Pol polyprotein precursor and an altered processing order compared to wild-type enzyme assessed in pseudovirions in transduced cells, FIV PR exchange mutants are much more susceptible to HIV-1 protease inhibitors than the wild-type FIV protease, overview
additional information
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generation of autolysis defective mutant enzymes
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additional information
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generation of different FIV PR mutants, by single point mutations and exchange of several amino acids comprising fragments, which show altered substrate specificity to Gag-Pol polyprotein precursor and an altered processing order compared to wild-type enzyme assessed in pseudovirions in transduced cells, FIV PR exchange mutants are much more susceptible to HIV-1 protease inhibitors than the wild-type FIV protease, overview
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