PDBsum entry 1qpl

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Isomerase PDB id
Protein chains
107 a.a. *
587 ×2
Waters ×14
* Residue conservation analysis

References listed in PDB file
Key reference
Title 32-Indolyl ether derivatives of ascomycin: three-Dimensional structures of complexes with fk506-Binding protein.
Authors J.W.Becker, J.Rotonda, J.G.Cryan, M.Martin, W.H.Parsons, P.J.Sinclair, G.Wiederrecht, F.Wong.
Ref. J Med Chem, 1999, 42, 2798-2804. [DOI no: 10.1021/jm9806042]
PubMed id 10425089
32-Indole ether derivatives of tacrolimus and ascomycin retain the potent immunosuppressive activity of their parent compounds but display reduced toxicity. In addition, their complexes with the 12-kDa FK506-binding protein (FKBP) form more stable complexes with the protein phosphatase calcineurin, the molecular target of these drugs. We have solved the three-dimensional structures of the FKBP complexes with two 32-indolyl derivatives of ascomycin. The structures of the protein and the macrolide are remarkably similar to those seen in the complexes with tacrolimus and ascomycin. The indole groups project away from the body of the complex, and multiple conformations are observed for the linkage to these groups as well as for a nearby peptide suggesting apparent flexibility in these parts of the structure. Comparison of these structures with that of the ternary complex of calcineurin, FKBP, and tacrolimus suggests that the indole groups interact with a binding site comprising elements of both the calcineurin alpha- and beta-chains and that this interaction is responsible for the increased stability of these complexes.
Secondary reference #1
Title A tacrolimus-Related immunosuppressant with biochemical properties distinct from those of tacrolimus.
Authors L.B.Peterson, J.G.Cryan, R.Rosa, M.M.Martin, M.B.Wilusz, P.J.Sinclair, F.Wong, J.N.Parsons, S.J.O'Keefe, W.H.Parsons, M.Wyvratt, N.H.Sigal, A.R.Williamson, G.J.Wiederrecht.
Ref. Transplantation, 1998, 65, 10-18.
PubMed id 9448137
Secondary reference #2
Title A tacrolimus-Related immunosuppressant with reduced toxicity.
Authors F.J.Dumont, S.Koprak, M.J.Staruch, A.Talento, G.Koo, C.Dasilva, P.J.Sinclair, F.Wong, J.Woods, J.Barker, J.Pivnichny, I.Singer, N.H.Sigal, A.R.Williamson, W.H.Parsons, M.Wyvratt.
Ref. Transplantation, 1998, 65, 18-26.
PubMed id 9448138
Secondary reference #3
Title Preparation and in vitro activities of naphthyl and indolyl ether derivatives of the fk-506 related immunosuppressive macrolide ascomycin.
Authors P.J.Sinclair, F.Wong, M.J.Staruch, G.Wiederrecht, W.H.Parsons, F.Dumont, M.Wyvratt.
Ref. bioorg med chem lett, 1996, 6, 2193.
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