8dw1 | pdb_00008dw1

Crystal structure of a host-guest complex with 5'-CTTAGTTATAACTAAG-3'

spinqualitylabelsall models 8dw1, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dw1 is a 3 chain structure with sequence from Moloney murine leukemia virus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8UN00_MLVMO Publication Abstract from PubMed Bleomycins constitute a family of anticancer natural products that bind DNA through intercalation of a C-terminal tail/bithiazole moiety and hydrogen-bonding interactions between the remainder of the drug and the minor groove. The clinical utility of the bleomycins is believed to result from single- and double-strand DNA cleavage mediated by the HOO-Fe(III) form of the drug. The bleomycins also serve as a model system to understand the nature of complex drug-DNA interactions that may guide future DNA-targeted drug discovery. In this study, the impact of the C-terminal tail on bleomycin-DNA interactions was investigated. Toward this goal, we determined two crystal structures of HOO-Co(III)*BLMA(2) "green" (a stable structural analogue of the active HOO-Fe(III) drug) bound to duplex DNA containing 5'-TAGTT, one in which the entire drug is bound (fully bound) and a second with only the C-terminal tail/bithiazole bound (partially bound). The structures reported here were captured by soaking HOO-Co(III)*BLMA(2) into preformed host-guest crystals including a preferred DNA-binding site. While the overall structure of DNA-bound BLMA(2) was found to be similar to those reported earlier at the same DNA site for BLMB(2), the intercalated bithiazole of BLMB(2) is "flipped" 180 relative to DNA-bound BLMA(2). This finding highlights an unidentified role for the C-terminal tail in directing the intercalation of the bithiazole. In addition, these analyses identified specific bond rotations within the C-terminal domain of the drug that may be relevant for its reorganization and ability to carry out a double-strand DNA cleavage event. Two distinct rotations of bithiazole DNA intercalation revealed by direct comparison of crystal structures of Co(III)*bleomycin A(2) and B(2) bound to duplex 5'-TAGTT sites.,Goodwin KD, Lewis MA, Long EC, Georgiadis MM Bioorg Med Chem. 2023 Jan 1;77:117113. doi: 10.1016/j.bmc.2022.117113. Epub 2022 , Dec 6. PMID:36516684 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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