PDBsum entry 1a58

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Isomerase PDB id
Protein chain
177 a.a.
Waters ×462

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Key reference
Title The X-Ray structure of a divergent cyclophilin from the nematode parasite brugia malayi.
Authors P.Taylor, A.P.Page, G.Kontopidis, H.Husi, M.D.Walkinshaw.
Ref. FEBS Lett, 1998, 425, 361-366. [DOI no: 10.1016/S0014-5793(98)00264-6]
PubMed id 9559680
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.
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.
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.
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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