4HAY

Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(K548E,K579Q)-Ran-RanBP1

4HAY の概要

• エントリーDOI: 10.2210/pdb4hay/pdb
• 関連するPDBエントリー: 4GMX 4GPT 4HAT 4HAU 4HAV 4HAW 4HAX 4HAZ 4HB0 4HB2 4HB3 4HB4
• 分子名称: GTP-binding nuclear protein Ran, Ran-specific GTPase-activating protein 1, Exportin-1, ... (9 entities in total)
• 機能のキーワード: heat repeat, nuclear export, ran-ranbp1, lmb, leptomycin b, protein transport-antibiotic complex, protein transport/antibiotic
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : P62826 P30822; Cytoplasm: P41920
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 159756.60

構造登録者

Sun, Q.,Chook, Y.M. (登録日: 2012-09-27, 公開日: 2013-01-09, 最終更新日: 2024-11-06)

主引用文献

Sun, Q.,Carrasco, Y.P.,Hu, Y.,Guo, X.,Mirzaei, H.,Macmillan, J.,Chook, Y.M.
Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1.
Proc.Natl.Acad.Sci.USA, 110:1303-1308, 2013

PubMed Abstract: The polyketide natural product Leptomycin B inhibits nuclear export mediated by the karyopherin protein chromosomal region maintenance 1 (CRM1). Here, we present 1.8- to 2.0-Å-resolution crystal structures of CRM1 bound to Leptomycin B and related inhibitors Anguinomycin A and Ratjadone A. Structural and complementary chemical analyses reveal an unexpected mechanism of inhibition involving covalent conjugation and CRM1-mediated hydrolysis of the natural products' lactone rings. Furthermore, mutagenesis reveals the mechanism of hydrolysis by CRM1. The nuclear export signal (NES)-binding groove of CRM1 is able to drive a chemical reaction in addition to binding protein cargoes for transport through the nuclear pore complex.

PubMed: 23297231
DOI: 10.1073/pnas.1217203110

実験手法

X-RAY DIFFRACTION (2.3 Å)