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PDBsum entry 4l1a
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Hydrolase/hydrolase inhibitor
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PDB id
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4l1a
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References listed in PDB file
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Key reference
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Title
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Crystallographic study of multi-Drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance.
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Authors
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Z.Liu,
R.S.Yedidi,
Y.Wang,
T.G.Dewdney,
S.J.Reiter,
J.S.Brunzelle,
I.A.Kovari,
L.C.Kovari.
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Ref.
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Biochem Biophys Res Commun, 2013,
437,
199-204.
[DOI no: ]
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PubMed id
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Abstract
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Lopinavir (LPV) is a second generation HIV-1 protease inhibitor. Drug resistance
has rapidly emerged against LPV since its US FDA approval on September 15, 2000.
Mutations at residues 32I, L33F, 46I, 47A, I54V, V82A, I84V, and L90M render the
protease drug resistant against LPV. We report the crystal structure of a
clinical isolate multi-drug resistant (MDR) 769 HIV-1 protease (resistant
mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) complexed with
LPV and the in vitro enzymatic IC50 of LPV against MDR 769. The structural and
functional studies demonstrate significant drug resistance of MDR 769 against
LPV, arising from reduced interactions between LPV and the protease target.
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