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 HIV mutation literature information.


  Human immunodeficiency virus type 1 proteinase resistance to symmetric cyclic urea inhibitor analogs.
 PMID: 9371337       1997       Antimicrobial agents and chemotherapy
Abstract: L90M had a lower Km than the wild type, whereas the G48V/L90M double mutant had an increased Km compared with that of the wild type, contributing to a 10-fold reduction in the k(cat)/Km.
Abstract: The proteinase gene of resistant virus was sequenced, and key mutations (G48V, V82A, I84V, L90M, and G48V/L90M) were introduced into clones used for the expression, purification, and further characterization of the enzyme.


  Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs.
 PMID: 9450540       1997       FEBS letters
Abstract: A model of saquinavir-resistant mutant protease G48V in complex with saquinavir predicts interactions similar to those found in the G48H crystal.


  Human immunodeficiency virus type 1 viral background plays a major role in development of resistance to protease inhibitors.
 PMID: 8643685       1996       Proc Natl Acad Sci U S A
Abstract: The clone-purified RF (G48V/A71T/V82A) virus, unlike the corresponding defective NL4-3 triple mutant, grew well and displayed cross-resistance to four distinct protease inhibitors.
Abstract: The predominant breakthrough virus contained the G48V/A71T/V82A protease mutations.


  In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: mutations, kinetics, and frequencies.
 PMID: 8648209       1996       The Journal of infectious diseases
Abstract: A Leu90-->Met exchange was the predominant resistance mutation in vivo; Gly48-->Val or doubly mutant virus was rarely observed.
Abstract: There was a good relationship between genotypic analysis of saquinavir resistance and data from virus assays, confirming that Leu90-->Met and Gly48-->Val are the essential exchanges in the proteinase that determine loss of sensitivity to this inhibitor.


  Reduced sensitivity to saquinavir: an update on genotyping from phase I/II trials.
 PMID: 8721556       1996       Antiviral research
Abstract: Genotypic resistance was defined by the Gly48-->Val and Leu90-->Met exchanges.


  Design, synthesis, and resistance patterns of MP-134 and MP-167, two novel inhibitors of HIV type 1 protease.
 PMID: 8825619       1996       AIDS research and human retroviruses
Abstract: An isoleucine-to-valine substitution at residue 84 (I84V) of the HIV-1 protease confers resistance to MP-134, whereas a glycine-to-valine substitution at residue 48 (G48V) confers resistance to MP-167.


  Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection.
 PMID: 8913459       1996       Antimicrobial agents and chemotherapy
Abstract: In addition to the changes at positions 82 and 90, we have identified M46L/I, G48V, and I54V substitutions in isolates derived from indinavir-treated patients.
Abstract: Patient human immunodeficiency virus type 1 (HIV-1) isolates that are resistant to protease inhibitors may contain amino acid substitutions L10I/V, M46L/I, G-48V, L63P, V82A/F/T, I84V, and L90M in the protease gene.


  Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex.
 PMID: 8969180       1996       The Journal of biological chemistry
Abstract: L90M, G48V, and L90M/G48V proteases have 1/20, 1/160, and 1/1000 the affinity for saquinavir compared to
Abstract: In contrast, G48V and L90M/G48V proteases had catalytic efficiency (kcat/Km) values with TLNF-PISP, RKIL-FLDG, and AETF-YVDG that were 1/10 to 1/20 the value of WT protease.
Abstract: In contrast, the dissociation rate constants for WT, L90M, G48V, and L90M/G48V proteases complexed with saquinavir were 0.0014, 0.019, 0.128, and 0.


  Rational approaches to resistance: using saquinavir.
 PMID: 8970671       1996       AIDS (London, England)
Abstract: Clinically, G48V is uncommon and the double mutation rare.
Abstract: RESISTANCE TO SAQUINAVIR: Resistance to saquinavir in vitro and in vivo is associated with mutations L90M and G48V in HIV protease.


  Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959.
 PMID: 7576926       1995       AIDS research and human retroviruses
Abstract: The primary event (Gly-48 to valine) occurs at the hinge of the flaps of the proteinase, thus hampering entry of the inhibitor to the active center and suggesting steric hindrance.



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