3ODL

Crystal structure of cyclophilin A in complex with Voclosporin Z-ISA247

3ODL の概要

• エントリーDOI: 10.2210/pdb3odl/pdb
• 関連するPDBエントリー: 3ODI
• 分子名称: Cyclophilin A, Voclosporin (3 entities in total)
• 機能のキーワード: calcineurin inhibition, calcineurin, cyclosporin, psoriasis, immunosuppressant, voclosporin, isomerase-immunosuppressant complex, isomerase/immunosuppressant
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 192691.39

構造登録者

Kuglstatter, A.,Stihle, M.,Benz, J.,Hennig, M. (登録日: 2010-08-11, 公開日: 2011-02-16, 最終更新日: 2023-12-06)

主引用文献

Kuglstatter, A.,Mueller, F.,Kusznir, E.,Gsell, B.,Stihle, M.,Thoma, R.,Benz, J.,Aspeslet, L.,Freitag, D.,Hennig, M.
Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin).
Acta Crystallogr.,Sect.D, 67:119-123, 2011

PubMed Abstract: E-ISA247 (voclosporin) is a cyclosporin A analogue that is in late-stage clinical development for the treatment of autoimmune diseases and the prevention of organ graft rejection. The X-ray crystal structures of E-ISA247 and its stereoisomer Z-ISA247 bound to cyclophilin A have been determined and their binding affinities were measured to be 15 and 61 nM, respectively, by fluorescence spectroscopy. The higher affinity of E-ISA247 can be explained by superior van der Waals contacts between its unique side chain and cyclophilin A. Comparison with the known ternary structure including calcineurin suggests that the higher immunosuppressive efficacy of E-ISA247 relative to cyclosporin A could be a consequence of structural changes in calcineurin induced by the modified E-ISA247 side chain.

PubMed: 21245533
DOI: 10.1107/S0907444910051905

実験手法

X-RAY DIFFRACTION (2.31 Å)