1YND

Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6A resolution

1YND の概要

• エントリーDOI: 10.2210/pdb1ynd/pdb
• 関連するPDBエントリー: 1NMK
• 分子名称: Peptidyl-prolyl cis-trans isomerase A, SANGLIFEHRIN A (3 entities in total)
• 機能のキーワード: beta sandwich, cyclophilin-ligand complex, cyclosporin, isomerase, rotamase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P62937
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38253.79

構造登録者

Kallen, J.,Sedrani, R.,Zenke, G.,Wagner, J. (登録日: 2005-01-24, 公開日: 2005-04-05, 最終更新日: 2023-08-23)

主引用文献

Kallen, J.,Sedrani, R.,Zenke, G.,Wagner, J.
Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6 A resolution.
J.Biol.Chem., 280:21965-21971, 2005

PubMed Abstract: Sanglifehrin A (SFA) is a novel immunosuppressant isolated from Streptomyces sp. that binds strongly to the human immunophilin cyclophilin A (CypA). SFA exerts its immunosuppressive activity through a mode of action different from that of all other known immunophilin-binding substances, namely cyclosporine A (CsA), FK506, and rapamycin. We have determined the crystal structure of human CypA in complex with SFA at 1.6 A resolution. The high resolution of the structure revealed the absolute configuration at all 17 chiral centers of SFA as well as the details of the CypA/SFA interactions. In particular, it was shown that the 22-membered macrocycle of SFA is deeply embedded in the same binding site as CsA and forms six direct hydrogen bonds with CypA. The effector domain of SFA, on the other hand, has a chemical and three-dimensional structure very different from CsA, already strongly suggesting different immunosuppressive mechanisms. Furthermore, two CypA.SFA complexes form a dimer in the crystal as well as in solution as shown by light scattering and size exclusion chromatography experiments. This observation raises the possibility that the dimer of CypA.SFA complexes is the molecular species mediating the immunosuppressive effect.

PubMed: 15772070
DOI: 10.1074/jbc.M501623200

実験手法

X-RAY DIFFRACTION (1.6 Å)