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PDBsum entry 2r5p
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References listed in PDB file
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Key reference
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Title
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The contribution of naturally occurring polymorphisms in altering the biochemical and structural characteristics of HIV-1 subtype c protease.
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Authors
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R.M.Coman,
A.H.Robbins,
M.A.Fernandez,
C.T.Gilliland,
A.A.Sochet,
M.M.Goodenow,
R.Mckenna,
B.M.Dunn.
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Ref.
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Biochemistry, 2008,
47,
731-743.
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PubMed id
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Abstract
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Fourteen subtype B and C protease variants have been engineered in an effort to
study whether the preexistent baseline polymorphisms, by themselves or in
combination with drug resistance mutations, differentially alter the biochemical
and structural features of the subtype C protease when compared with those of
subtype B protease. The kinetic studies performed in this work showed that the
preexistent polymorphisms in subtype C protease, by themselves, do not provide
for a greater level of resistance. Inhibition analysis with eight clinically
used protease inhibitors revealed that the natural polymorphisms found in
subtype C protease, in combination with drug resistance mutations, can influence
enzymatic catalytic efficiency and inhibitor resistance. Structural analyses of
the subtype C protease bound to nelfinavir and indinavir showed that these
inhibitors form similar interactions with the residues in the active site of
subtype B and C proteases. It also revealed that the naturally occurring
polymorphisms could alter the position of the outer loops of the subtype C
protease, especially the 60's loop.
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