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PDBsum entry 1bvg
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Aspartyl protease
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PDB id
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1bvg
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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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Three-Dimensional solution structure of the HIV-1 protease complexed with dmp323, A novel cyclic urea-Type inhibitor, Determined by nuclear magnetic resonance spectroscopy.
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Authors
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T.Yamazaki,
A.P.Hinck,
Y.X.Wang,
L.K.Nicholson,
D.A.Torchia,
P.Wingfield,
S.J.Stahl,
J.D.Kaufman,
C.H.Chang,
P.J.Domaille,
P.Y.Lam.
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Ref.
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Protein Sci, 1996,
5,
495-506.
[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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The three-dimensional solution structure of the HIV-1 protease homodimer, MW
22.2 kDa, complexed to a potent, cyclic urea-based inhibitor, DMP323, is
reported. This is the first solution structure of an HIV protease/inhibitor
complex that has been elucidated. Multidimensional heteronuclear NMR spectra
were used to assemble more than 4,200 distance and angle constraints. Using the
constraints, together with a hybrid distance geometry/simulated annealing
protocol, an ensemble of 28 NMR structures was calculated having no distance or
angle violations greater than 0.3 A or 5 degrees, respectively. Neglecting
residues in disordered loops, the RMS deviation (RMSD) for backbone atoms in the
family of structures was 0.60 A relative to the average structure. The
individual NMR structures had excellent covalent geometry and stereochemistry,
as did the restrained minimized average structure. The latter structure is
similar to the 1.8-A X-ray structure of the protease/DMP323 complex (Chang CH et
al., 1995, Protein Science, submitted); the pairwise backbone RMSD calculated
for the two structures is 1.22 A. As expected, the mismatch between the
structures is greatest in the loops that are disordered and/or flexible. The
flexibility of residues 37-42 and 50-51 may be important in facilitating
substrate binding and product release, because these residues make up the
respective hinges and tips of the protease flaps. Flexibility of residues 4-8
may play a role in protease regulation by facilitating autolysis.
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