6a3e | pdb_00006a3e

MVM NES mutant Nm15 in complex with CRM1-Ran-RanBP1

spinqualitylabelsall models 6a3e, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6a3e is a 4 chain structure with sequence from Homo sapiens, Minute virus of mice and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: GTP, 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 Introduction: Peptides can be rationally designed as non-covalent inhibitors for molecularly targeted therapy. However, it remains challenging to efficiently deliver the peptides into the targeted cells, which often severely affects their therapeutic efficiency. Methods: Herein, we created a novel non-covalent peptide inhibitor against nuclear export factor CRM1 by a structure-guided drug design method and targetedly delivered the peptide into cancer cells by a nanoparticle-mediated gene expression system for use as a cancer therapy. Results: The nuclear export signal (NES)-optimized CRM1 peptide inhibitor colocalized with CRM1 to the nuclear envelope and inhibited nuclear export in cancer cell lines in vitro. The crystal structures of the inhibitors complexed with CRM1 were solved. In contrast to the covalent inhibitors, the peptides were similarly effective against cells harboring the CRM1 C528S mutation. Moreover, a plasmid encoding the peptides was delivered by a iRGD-modified nanoparticle to efficiently target and transfect the cancer cells in vivo after intravenous administration. The peptides could be selectively expressed in the tumor, resulting in the efficient inhibition of subcutaneous melanoma xenografts without obvious systemic toxicity. Discussion: This work provides an effective strategy to design peptide-based molecularly targeted therapeutics, which could lead to the development of future targeted therapy. Cancer Therapy with Nanoparticle-Medicated Intracellular Expression of Peptide CRM1-Inhibitor.,Sui M, Xiong M, Li Y, Zhou Q, Shen X, Jia D, Gou M, Sun Q Int J Nanomedicine. 2021 Apr 14;16:2833-2847. doi: 10.2147/IJN.S266398., eCollection 2021. PMID:33883894 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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