1mnv

Actinomycin D binding to ATGCTGCAT

spinqualitylabelsall models 1mnv, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1mnv is a 4 chain structure with sequence from "actinomyces_antibioticus"_waksman_and_woodruff_1941 "actinomyces antibioticus" waksman and woodruff 1941. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: DVA, MVA, PXZ, SAR Related: 1a7z, 209d, 1unm, 1i3w, 1a7y, 1fja, 173d, 2d55, 1dsc, 1l1v, 316d, 1dsd, 1unj, 1ovf, 1qfi Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The potent anticancer drug actinomycin D (ActD) acts by binding to DNA GpC sequences, thereby interfering with essential biological processes including replication, transcription and topoisomerase. Certain neurological diseases are correlated with expansion of (CTG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single base pair. In order to characterize the binding of ActD to CTG triplet repeat sequences, we carried out heat denaturation and CD analyses, which showed that adjacent GpC sequences flanking a T:T mismatch are preferred ActD-binding sites, and that ActD binding results in a conformational transition to A-type structure. The structural basis of the strong binding of ActD to neighboring GpC sites flanking a T:T mismatch was provided by the crystal structure of ActD bound to ATGCTGCAT, which contains a CTG triplet sequence. Binding of two ActD molecules to GCTGC causes a kink in the DNA helix. In addition, using a synthetic self-priming DNA model, 5'-(CAG)4(CTG)(16)-3', we observed that ActD can trap the cruciform or duplexes of (CTG)n and interfere with the expansion process of CTG triplet repeats as shown by gel electrophoretic expansion assay. Our results may provide the possible biological consequence of ActD bound to CTG triplet repeat sequences. Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases.,Hou MH, Robinson H, Gao YG, Wang AH Nucleic Acids Res. 2002 Nov 15;30(22):4910-7. PMID:12433994 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA