 |
PDBsum entry 1a9m
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Aspartyl protease
|
PDB id
|
|
|
|
1a9m
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of a g48h mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs.
|
|
|
Authors
|
|
L.Hong,
X.J.Zhang,
S.Foundling,
J.A.Hartsuck,
J.Tang.
|
|
|
Ref.
|
|
Febs Lett, 1997,
420,
11-16.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The crystal structure of human immunodeficiency virus type 1 (HIV-1) protease
mutant G48H with peptidic inhibitor U-89360E is described. Comparison with
wild-type protease-inhibitor complex shows that mutation of flap residue 48 to
histidine allows stabilizing van der Waals contacts between the side chains of
His48 and Phe53 as well as between His48 and the P2' and P3' inhibitor subsites.
The flap region is less mobile than in the wild-type enzyme. A model of
saquinavir-resistant mutant protease G48V in complex with saquinavir predicts
interactions similar to those found in the G48H crystal. Energetic calculations
confirm the similarity of the His48 and Val48 interactions.
|
|
|
|
|
|
|
|
Figure 2.
Fig. 2. Stereo view of the structural relationship of the
inhibitor molecule and protease residues 48A, 53A, 48B and 53B.
Electron densities from the 2|F[o]|−|F[c]| map are shown at 1
σ contour level. A C[α] to C[α] backbone trace for residues
48 to 53 is included. The position of the side chain of residue
B53 in the wild-type structure is also shown (orange).
|
|
Figure 4.
Fig. 4. Van der Waals interaction of Phe^A53, Val^A48 and
the P[3] subsite of saquinavir in the structural model of HIV-1
mutant protease G48V complex with saquinavir. The saquinavir
positions in the wild-type crystal structure (orange) and of the
G48V mutant model structure (yellow) are both shown. There is
a 30° rotation of the saquinavir P[3] planar quinoline group
(double ring) in the G48V complex compared to that in the
wild-type enzyme. This change appears to be a result of its
interaction with Val^48. The van der Waals interaction between
Val^48 and Phe^53 is shown but the view does not minimize
overlap of the surfaces.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
Febs Lett
(1997,
420,
11-16)
copyright 1997.
|
|
|
|
|
|
|
