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Literature summary for 3.4.23.16 extracted from

  • Tie, Y.; Boross, P.I.; Wang, Y.F.; Gaddis, L.; Liu, F.; Chen, X.; Tozser, J.; Harrison, R.W.; Weber, I.T.
    Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs (2005), FEBS J., 272, 5265-5277.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.23.16

Cloned(Commentary)

Cloned (Comment) Organism
expression of wild-type enzyme, mutant V82A enzyme, and mutant I84V enzyme Human immunodeficiency virus 1

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant wild-type enzyme, mutant V82A enzyme, and mutant I84V enzyme in complex with substrate analogue inhibitors, 5 mg/ml protein mixed with inhibitor in a 20fold molar excess, incubation at 4°C for 1 h, hanging drop vapour diffusion method, 24°C, equal volumes of protein and reservoir solutions, the latter containing 0.1 M sodium acetate/citrate phosphate buffer, pH 4.2-5.0, 5% v/v DMSO, 0-5% v/v dioxane, 0.4-1.2 M sodium chloride, and 15-40% w/v saturated ammonium sulfate, X-ray diffraction structure determination and analysis at 1.10-1.54 A resolution Human immunodeficiency virus 1

Protein Variants

Protein Variants Comment Organism
Q7K/L33I/L63I/C67A/I84A/C95A site-directed mutagenesis, mutations Q7K, L33I, and L63I minimizes enzyme autoproteolysis, mutations C67A and C95A prevent cysteine thiol oxidation, the I84A mutation confers drug-resistance Human immunodeficiency virus 1
Q7K/L33I/L63I/C67A/V82A/C95A site-directed mutagenesis, mutations Q7K, L33I, and L63I minimizes enzyme autoproteolysis, mutations C67A and C95A prevent cysteine thiol oxidation, the V823A mutation confers drug-resistance Human immunodeficiency virus 1

Inhibitors

Inhibitors Comment Organism Structure
Ace-T-I-Nle-r-Nle-Q-R substrate analogue, competitive inhibition of the HIV-1 protease, mimicks the p2-NC cleavage site Human immunodeficiency virus 1
E-R-Q-A-N-r-F-L-G-K-I substrate analogue, competitive inhibition of the HIV-1 protease, mimicks the NC/p1 cleavage site Human immunodeficiency virus 1
additional information molecular basis for substrate recognition and drug resistance, structure analysis of substrate analogue inhibitors bound to wild-type enzyme, mutant V82A enzyme, and mutant I84V enzyme, overview Human immunodeficiency virus 1
R-P-G-N-F-r-L-Q-S-R-P substrate analogue, competitive inhibition of the HIV-1 protease, mimicks the pI-p6 cleavage site Human immunodeficiency virus 1
R-V-L-r-F-E-A-Nle substrate analogue, competitive inhibition of the HIV-1 protease, mimicks the CA/p2 cleavage site Human immunodeficiency virus 1
V-S-F-N-F-r-P-Q-I-T-K-K substrate analogue, competitive inhibition of the HIV-1 protease, mimicks the p6pol-PR cleavage site Human immunodeficiency virus 1

Organism

Organism UniProt Comment Textmining
Human immunodeficiency virus 1
-
 i.e. HIV-1
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification the enzyme performs autoproteolysis which is minimized by mutations Q7K, L33I, and L63I Human immunodeficiency virus 1

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type enzyme, mutant V82A enzyme, and mutant I84V enzyme Human immunodeficiency virus 1

Renatured (Commentary)

Renatured (Comment) Organism
recombinant wild-type enzyme, mutant V82A enzyme, and mutant I84V enzyme Human immunodeficiency virus 1

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Gag precursor protein + H2O five different cleavage sites, the p2-NC-site is the first, the CA/p2 the last one in sequential processing of the precursor Human immunodeficiency virus 1 ?
-
 ?
Lys-Ala-Arg-Val-Leu-4-nitro-Phe-Glu-Ala-Nle-Gly + H2O i.e. substrate L6525, the peptide substrate contains the CA-p2 cleavage site Human immunodeficiency virus 1 Lys-Ala-Arg-Val-Leu + 4-nitro-Phe-Glu-Ala-Nle-Gly
-
 ?
additional information molecular basis for substrate recognition and drug resistance Human immunodeficiency virus 1 ?
-
 ?

Subunits

Subunits Comment Organism
dimer the enzyme is active as homodimer Human immunodeficiency virus 1

Synonyms

Synonyms Comment Organism
HIV-1 protease
-
 Human immunodeficiency virus 1
PR
-
 Human immunodeficiency virus 1

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
5
-
 assay at Human immunodeficiency virus 1

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000024
-
 R-V-L-r-F-E-A-Nle mutant V82A enzyme Human immunodeficiency virus 1
0.000075
-
 R-V-L-r-F-E-A-Nle wild-type enzyme Human immunodeficiency virus 1
0.000275
-
 R-V-L-r-F-E-A-Nle mutant I84V enzyme Human immunodeficiency virus 1
0.00053
-
 Ace-T-I-Nle-r-Nle-Q-R mutant V82A enzyme Human immunodeficiency virus 1
0.00217
-
 Ace-T-I-Nle-r-Nle-Q-R wild-type enzyme Human immunodeficiency virus 1
0.013
-
 Ace-T-I-Nle-r-Nle-Q-R mutant I84V enzyme Human immunodeficiency virus 1
0.0221
-
 V-S-F-N-F-r-P-Q-I-T-K-K wild-type enzyme Human immunodeficiency virus 1
0.0282
-
 R-P-G-N-F-r-L-Q-S-R-P mutant V82A enzyme Human immunodeficiency virus 1
0.0363
-
 V-S-F-N-F-r-P-Q-I-T-K-K mutant V82A enzyme Human immunodeficiency virus 1
0.0466
-
 V-S-F-N-F-r-P-Q-I-T-K-K mutant I84V enzyme Human immunodeficiency virus 1
0.0967
-
 R-P-G-N-F-r-L-Q-S-R-P wild-type enzyme Human immunodeficiency virus 1
0.5
-
 R-P-G-N-F-r-L-Q-S-R-P above, mutant I84V enzyme Human immunodeficiency virus 1
0.5
-
 E-R-Q-A-N-r-F-L-G-K-I above, wild-type enzyme, mutant V82A enzyme, and mutant I84V enzyme Human immunodeficiency virus 1