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PDBsum entry 4hax
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Protein transport/antibiotic
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PDB id
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4hax
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Contents |
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1017 a.a.
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200 a.a.
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131 a.a.
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References listed in PDB file
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Key reference
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Title
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Nuclear export inhibition through covalent conjugation and hydrolysis of leptomycin b by crm1.
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Authors
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Q.Sun,
Y.P.Carrasco,
Y.Hu,
X.Guo,
H.Mirzaei,
J.Macmillan,
Y.M.Chook.
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Ref.
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Proc Natl Acad Sci U S A, 2013,
110,
1303-1308.
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PubMed id
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Abstract
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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 cargos for
transport through the nuclear pore complex.
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