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PDBsum entry 1fgl
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Isomerase/viral protein
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PDB id
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1fgl
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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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Cyclophilin a complexed with a fragment of HIV-1 gag protein: insights into HIV-1 infectious activity.
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Authors
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Y.Zhao,
Y.Chen,
M.Schutkowski,
G.Fischer,
H.Ke.
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Ref.
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Structure, 1997,
5,
139-146.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Cyclophilin A (CyPA), a receptor of the immunosuppressive drug
cyclosporin A, catalyzes the cis-trans isomerization of peptidyl-prolyl bonds
and is required for the infectious activity of human immunodeficiency virus type
1 (HIV-1). The crystal structure of CyPA complexed with a fragment of the HIV-1
gag protein should provide insights into the nature of CyPA-gag interactions and
may suggest a role for CyPA in HIV-1 infectious activity. RESULTS: The crystal
structure of CyPA complexed with a 25 amino acid peptide of HIV-1 gag capsid
protein (25-mer) was determined and refined to an R factor of 0.195 at 1.8 A
resolution. The sequence Ala88-Gly89-Pro90-Ile91 of the gag fragment is the
major portion to bind to the active site of CyPA. Two residues of the 25-mer
(Pro90-Ile91) bind to CyPA in a similar manner to two residues (Pro-Phe) of the
CyPA substrate, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (AAPF). However, the
N-terminus of the 25-mer (Ala88-Gly89) exhibits a different hydrogen-bonding
pattern and molecular conformation than AAPF. The peptidyl-prolyl bond between
Gly89 and Pro90 of the 25-mer has a trans conformation, in contrast to the cis
conformation observed in other known CyPA-peptide complexes. The residue
preceding proline, Gly89, has an unfavorable backbone conformation usually only
adopted by glycine. CONCLUSIONS: The unfavorable backbone conformation of Gly89
of the gag 25-mer fragment suggests that binding between HIV-1 gag protein and
CyPA requires a special sequence, Gly-Pro. Thus, in HIV-1 infectivity, CyPA is
likely to function as a chaperone, rather than as a cis-trans isomerase.
However, the observation of similarities between the C termini of the 25-mer and
the substrate AAPF means that the involvement of the cis-trans isomerase
activity of CyPA cannot be completely ruled out.
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Figure 1.
Figure 1. Crystal structure of CyPA complexed with a
fragment of HIV-1 gag protein. (a) Molecular surface charge
distribution: the positively charged regions are shown in blue
and negatively charged regions are in red. The 25-mer of gag
capsid protein is represented in green and its sidechains are in
yellow. (Figure drawn using GRASP [49].) (b) Ribbon
representation: helices are shown in red, b strands in orange
and loops in blue. Residues of the 25-mer are shown as a yellow
stick model. (Figure plotted using the program MOLSCRIPT [50]
and Raster3D [51].)
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1997,
5,
139-146)
copyright 1997.
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