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PDBsum entry 2fxd
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References listed in PDB file
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Key reference
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Title
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X-Ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir.
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Authors
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H.E.Klei,
K.Kish,
P.F.Lin,
Q.Guo,
J.Friborg,
R.E.Rose,
Y.Zhang,
V.Goldfarb,
D.R.Langley,
M.Wittekind,
S.Sheriff.
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Ref.
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J Virol, 2007,
81,
9525-9535.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Atazanavir, which is marketed as REYATAZ, is the first human immunodeficiency
virus type 1 (HIV-1) protease inhibitor approved for once-daily administration.
As previously reported, atazanavir offers improved inhibitory profiles against
several common variants of HIV-1 protease over those of the other peptidomimetic
inhibitors currently on the market. This work describes the X-ray crystal
structures of complexes of atazanavir with two HIV-1 protease variants, namely,
(i) an enzyme optimized for resistance to autolysis and oxidation, referred to
as the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant
of the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors,
referred to as the inhibitor-resistant mutant. In these two complexes,
atazanavir adopts distinct bound conformations in response to the V82F
substitution, which may explain why this substitution, at least in isolation,
has yet to be selected in vitro or in the clinic. Because of its nearly
symmetrical chemical structure, atazanavir is able to make several analogous
contacts with each monomer of the biological dimer.
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