4hax | pdb_00004hax

Crystal structure of CRM1 inhibitor Ratjadone A in complex with CRM1(K579A)-Ran-RanBP1

spinqualitylabelsall models 4hax, resolution 2.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hax is a 3 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, EDO, GNP, GOL, MG, RJA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function XPO1_YEAST Receptor for the leucine-rich nuclear export signal (NES). Publication Abstract from PubMed 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-A-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 cargos for transport through the nuclear pore complex. Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1.,Sun Q, Carrasco YP, Hu Y, Guo X, Mirzaei H, Macmillan J, Chook YM Proc Natl Acad Sci U S A. 2013 Jan 7. PMID:23297231 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Exportin 3D structures GTP-binding protein 3D structures

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