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PDBsum entry 1a8g
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Hydrolase/hydrolase inhibitor
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PDB id
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1a8g
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Contents |
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* Residue conservation analysis
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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 structure and conformational dynamics of the HIV-1 protease in complex with the inhibitor sdz283-910: agreement of time-Resolved spectroscopy and molecular dynamics simulations.
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Authors
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S.Ringhofer,
J.Kallen,
R.Dutzler,
A.Billich,
A.J.Visser,
D.Scholz,
O.Steinhauser,
H.Schreiber,
M.Auer,
A.J.Kungl.
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Ref.
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J Mol Biol, 1999,
286,
1147-1159.
[DOI no: ]
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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 were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
97%.
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Abstract
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Based on the X-ray structure of the human immunodeficiency virus type-1 (HIV-1)
protease in complex with the statine-derived inhibitor SDZ283-910, a 542 ps
molecular dynamics trajectory was computed. For comparison with the 805 ps
trajectory obtained for the uncomplexed enzyme, the theoretical fluorescence
anisotropy decay of the unliganded protease and the inhibitor complex was
calculated from the trajectories of the Trp6A/Trp6B and Trp42A/Trp42B transition
dipole moments. This enabled us to directly compare the simulated data with the
experimental picosecond time-resolved fluorescence data. Fitting both
experimental and simulated data to the Kohlrausch-Williams-Watts (KWW) function
exp(-t/tauk)beta revealed a very good agreement for the uncomplexed protease as
well as for the SDZ283-910 complex. Binding of the inhibitor induced a faster
decay of both the experimental and the computed protease fluorescence anisotropy
decay. By this integrative approach, the atomic detail of inhibitor-induced
changes in the conformational dynamics of the HIV-1 protease was experimentally
verified and will be used for further inhibitor optimisation.
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Figure 1.
Figure 1. Structure of the HIV-1 protease/SDZ283-910
inhibitor complex, indicating the position of the inhibitor as
well as of the tryptophan residues.
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Figure 2.
Figure 2. Structure of SDZ283-910. Also included are the
building blocks used for generating the MD input.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
286,
1147-1159)
copyright 1999.
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