4f1i

Crystal structure of SeMet TDP2 from Caenorhabditis elegans

spinqualitylabelsall models 4f1i, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4f1i is a 1 chain structure with sequence from Caeel. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL NonStd Res: MSE Related: 4fpv, 4f1h, 4fva, 4gew Gene: Y63D3A.4 (CAEEL) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TYDP2_CAEEL] DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals (By similarity). Publication Abstract from PubMed The DNA-repair enzyme Tdp2 resolves 5'-phosphotyrosyl DNA adducts and mediates resistance to anticancer drugs that target covalent topoisomerase-DNA complexes. Tdp2 also participates in key signaling pathways during development and tumorigenesis and cleaves a protein-RNA linkage during picornavirus replication. The crystal structure of zebrafish Tdp2 bound to DNA reveals a deep, narrow basic groove that selectively accommodates the 5' end of single-stranded DNA in a stretched conformation. The crystal structure of the full-length Caenorhabditis elegans Tdp2 shows that this groove can also accommodate an acidic peptide stretch in vitro, with glutamate and aspartate side chains occupying the DNA backbone phosphate-binding sites. This extensive molecular mimicry suggests a potential mechanism for autoregulation and interaction of Tdp2 with phosphorylated proteins in signaling. Our study provides a framework to interrogate functions of Tdp2 and develop inhibitors for chemotherapeutic and antiviral applications. Structural basis for recognition of 5'-phosphotyrosine adducts by Tdp2.,Shi K, Kurahashi K, Gao R, Tsutakawa SE, Tainer JA, Pommier Y, Aihara H Nat Struct Mol Biol. 2012 Dec;19(12):1372-7. doi: 10.1038/nsmb.2423. Epub 2012, Oct 28. PMID:23104058 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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