4hb0 | pdb_00004hb0

Crystal structure of CRM1 inhibitor Leptomycin B in complex with CRM1(K541Q,K542Q,R543S,K545Q,K548Q,K579Q)-Ran-RanBP1

spinqualitylabelsall models 4hb0, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hb0 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. Method: X-ray diffraction, Resolution 2.2Å Ligands: CL, GNP, LBF, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function YRB1_YEAST Important for the export of protein containing nuclear export signal (NES) out of the nucleus. Stimulates the GTPase activity of GSP1 and GSP2. 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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