Analysis of HIV-1 CRF_01 A/E protease inhibitor resistance: structural determinants for maintaining sensitivity and developing resistance to atazanavir.
Abstract: This structure also explains why the I50L and I84V mutations are important in decreasing the binding affinity of atazanavir.
Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors.
PMID: 16127059
2005
Antimicrobial agents and chemotherapy
Abstract: Additional biophysical and enzyme kinetics experiments show I50L/A71V protease is a stable enzyme with catalytic activity that is slightly reduced (34%) relative to the WT.
Abstract: Computational modeling reveals that the unique resistance phenotype of I50L/A71V protease likely originates from bulky tert-butyl groups at P2 and P2' (specific to atazanavir) that sterically clash with methyl groups on residue L50.
Abstract: Remarkably, we find that all of the PIs have 2- to 10-fold increased affinities for I50L/A71V protease, except for atazanavir.
Abstract: The results are also manifested by thermal stabili
Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones.
PMID: 16127058
2005
Antimicrobial agents and chemotherapy
Abstract: A unique phenotypic profile has been associated with viruses containing the I50L substitution, which produces ATV-specific resistance and increased susceptibility to most other approved HIV protease inhibitors (PIs).
Abstract: In this report, a direct effect of I50L on the susceptibility to the PI class is described.
Abstract: Moreover, the I50L substitution functions to increase PI susceptibility even in the presence of other primary and secondary PI resistance substitutions.
Abstract: Substitution of leucine for isoleucine at residue 50 (I50L) of human immunodeficiency virus (HIV) protease
Resistance to HIV protease inhibitors: mechanisms and clinical consequences.
Abstract: Specific changes are characteristically linked to resistance to each of these compounds (i.e., D30N for nelfinavir, I50L for atazanavir or I50V for amprenavir).
The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients.
Abstract: For treatment-naive patients receiving atazanavir who experience virologic rebound, the I50L mutation in HIV protease arises, which does not confer cross-resistance to other protease inhibitors.
Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens.
PMID: 15122516
2004
The Journal of infectious diseases
Abstract
Abstract: Clinical isolates obtained from PI-naive patients designated as experiencing virologic failure while receiving ATV-containing regimens contained a unique isoleucine-to-leucine substitution at amino acid residue 50 (I50L) of the HIV-1 protease.
Abstract: Comparison of viruses bearing I50L with those bearing I50V revealed specific resistance to ATV and amprenavir, respectively, with no evidence of cross-resistance.
Abstract: The I50L substitution, observed in all isolates exhibiting phenotypic resistance to ATV, emerged in a variety of different backgrounds and was most frequently accompanied by A71V, K45R, and/or G73S.
HIV mutation literature information.
PMID: 
2006
Biochemistry
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