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Literature summary for 3.4.23.16 extracted from

  • Sayer, J.M.; Liu, F.; Ishima, R.; Weber, I.T.; Louis, J.M.
    Effect of the active-site D25N mutation on the structure, stability and ligand binding of the mature HIV-1 protease (2008), J. Biol. Chem., 283, 13459-13470.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
vapor diffusion hanging drop method, mutant enzyme complexed to darunavir or acetyl-Thr-Ile-Nle-r-Nle-Gln-Arg-NH2 Human immunodeficiency virus 1

Protein Variants

Protein Variants Comment Organism
D25N mutation increases the equilibrium dimer dissociation constant by a factor of more than 100fold relative to wild-type. In the absence of inhibitor, NMR studies reveal clear structural differences between wild-type and mutant enzyme in the relatively mobile P1 loop (residues 79-83) and flap regions, and differential scanning calorimetric analyses show that the mutation lowers the stabilities of both the monomer and dimer folds by 5 and 7.3°C, respectively. Complexation with acetyl-Thr-Ile-Nle-r-Nle-Gln-Arg-NH2 stabilizes both dimers, the effect on their Tm is smaller for the mutant enzyme (6.2°C) than for wild-type enzyme (8.7°C). The Tm of mutant enzyme/darunavir increases by only 3°C relative to free mutant enzyme, as compared with a 22°C increase for wild-type enzyme/darunavir. Mutation increases the ligand dissociation constant of mutant enzyme/darunavir by a factor of about 1000000 relative to wild-type enzyme/darunavir Human immunodeficiency virus 1

Inhibitors

Inhibitors Comment Organism Structure
darunavir
-
Human immunodeficiency virus 1

Organism

Organism UniProt Comment Textmining
Human immunodeficiency virus 1
-
-
-

Synonyms

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

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
additional information
-
complexation with acetyl-Thr-Ile-Nle-r-Nle-Gln-Arg-NH2 stabilizes dimers of wild-type enzyme and mutant enzyme D25N. The effect on their Tm is smaller for the mutant enzyme (6.2°C) than for wild-type enzyme (8.7°C). The Tm of mutant enzyme-darunavir complex increases by 3°C relative to free mutant enzyme, as compared with a 22°C increase for wild-type enzyme-darunavir complex Human immunodeficiency virus 1