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PDBsum entry 1awr
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Complex (isomerase/peptide)
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PDB id
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1awr
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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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Crystal structure of cyclophilin a complexed with a binding site peptide from the HIV-1 capsid protein.
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Authors
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F.F.Vajdos,
S.Yoo,
M.Houseweart,
W.I.Sundquist,
C.P.Hill.
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Ref.
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Protein Sci, 1997,
6,
2297-2307.
[DOI no: ]
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PubMed id
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Abstract
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The cellular protein, cyclophilin A (CypA), is incorporated into the virion of
the type 1 human immunodeficiency virus (HIV-1) via a direct interaction with
the capsid domain of the viral Gag polyprotein. We demonstrate that the capsid
sequence 87His-Ala-Gly-Pro-Ile-Ala92 (87HAGPIA92) encompasses the primary
cyclophilin A binding site and present an X-ray crystal structure of the
CypA/HAGPIA complex. In contrast to the cis prolines observed in all previously
reported structures of CypA complexed with model peptides, the proline in this
peptide, Pro 90, binds the cyclophilin A active site in a trans conformation. We
also report the crystal structure of a complex between CypA and the hexapeptide
HVGPIA, which also maintains the trans conformation. Comparison with the
recently determined structures of CypA in complexes with larger fragments of the
HIV-1 capsid protein demonstrates that CypA recognition of these hexapeptides
involves contacts with peptide residues Ala(Val) 88, Gly 89, and Pro 90, and is
independent of the context of longer sequences.
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Figure 6.
Fig. 6. A: HAGPIA and CypA are shown in CPK and ribbon representa-
tions, respectively. B: Orthogonal view. C: The molecular surface of CypA
is colored gray and green according to curvature. CypA residues that in-
teract with HAGPIA are shown, and residues that hydrogen bond (magen-
ta) HAGPIA re in yellow. H drogen bonds are defined as acceptor
to donor distances of less than 3.3
x.
The HAGPIA N-terminal histidine
and C-terminal alanine are labeled in For clarity, the side chains f the
histidine and isoleucine have been omitted. Two ordered water
that form bridging hydrogen bonds between peptide main chain
and CypA active site residues are shown as blue spheres.
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Figure 7.
Fig. 7. Superposition of HAGPIA and peptides refined in the
pseudo (P4~)-cell. CypA CA atoms (residues 2-165) were overlapped by
least squares (Kabsch, 976). CypA residues that hydrogen bond pep-
tide ligands are HAGPIA (magenta), (cyan). Ala/Val 88
and the peptide proline residues are labeled.
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The above figures are
reprinted
from an Open Access publication published by the Protein Society:
Protein Sci
(1997,
6,
2297-2307)
copyright 1997.
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