4hb3 | pdb_00004hb3

Crystal structure of CRM1(T539S)-Ran-RanBP1 with weakly bound unmodeled Leptomycin B

spinqualitylabelsall models 4hb3, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hb3 is a 3 chain structure with sequence from Atcc 18824 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, GNP, MG Related: 4gmx, 4gpt, 4hat, 4hau, 4hav, 4haw, 4hax, 4hay, 4haz, 4hb0, 4hb2, 4hb4 Gene: RAN, ARA24, OK/SW-cl.81 (HUMAN), YRB1, CST20, HTN1, SFO1, YDR002W, YD8119.08 (ATCC 18824), CRM1, KAP124, XPO1, YGR218W, G8514 (ATCC 18824) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RAN_HUMAN] GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2. Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases. [XPO1_YEAST] Receptor for the leucine-rich nuclear export signal (NES). [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.

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