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PDBsum entry 1a58
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References listed in PDB file
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Key reference
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Title
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The X-Ray structure of a divergent cyclophilin from the nematode parasite brugia malayi.
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Authors
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P.Taylor,
A.P.Page,
G.Kontopidis,
H.Husi,
M.D.Walkinshaw.
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Ref.
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Febs Lett, 1998,
425,
361-366.
[DOI no: ]
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PubMed id
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Abstract
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A structure of residues 1-177 of the cyclophilin domain of a large divergent
cyclophilin from the filarial nematode parasite Brugia malayi has been
crystallised and solved in two different crystal forms. The active site has a
similar structure to that of human cyclophilin A. Two of the 13 residues
important in forming the human cyclophilin A/cyclosporin A complex are altered
in the B. malayi cyclophilin and explain the relatively poor inhibition of
peptidyl prolyl isomerase activity by cyclosporin A.
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Figure 2.
Fig. 2. Overlay of bmCyp-1 (pale grey) with hCypA (dark
grey) from a least squares fit using corresponding backbone
atoms. The octapeptide insert (51-KISGKPLH-58) in bmCyp-1 is
highlighted. The eight β-strands and two longer α-helices are
labelled. Positions of selected bmCyp-1 residues are also
indicated.
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Figure 4.
Fig. 4. A: Stereo view of an overlay of the active site of
bmCyp-1 (filled bonds) with hCypA (unfilled bonds) showing the
side chains of the 13 residues known to be involved in substrate
and inhibitor binding of hCypA. The hydrogen bond from the amino
nitrogen atom of K114 to the carbonyl O of G83 is shown as a
thin line. B: Stereo view of the active site of bmCyp-1 (filled
bonds) with the cyclic peptide cyclosporin A (CsA). CsA
coordinates are from the hCypA/CsA complex [18] and positioned
from the least squares fit used in A. The side chain of K114 in
the bmCyp-1 structure acts as a gate to block access to the
‘Abu-pocket' which is a deep accessible cleft in the hCypA
structure. C: Stereo view of the active site of bmCyp-1 (filled
bonds) showing the position M46 (unfilled bonds) from a
crystallographically related neighbouring molecule. M46 forms
van der Waals contacts with F71, M72, F124, L133 and H137 and
suggests that the hydrophobic active site of cyclophilins may
accommodate a range of large hydrophobic groups.
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
Febs Lett
(1998,
425,
361-366)
copyright 1998.
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