8dw1: Difference between revisions
New page: '''Unreleased structure''' The entry 8dw1 is ON HOLD Authors: Georgiadis, M.M. Description: Crystal structure of a host-guest complex with 5''-CTTAGTTATAACTAAG-3'' [[Category: Unreleas... |
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The | ==Crystal structure of a host-guest complex with 5'-CTTAGTTATAACTAAG-3'== | ||
<StructureSection load='8dw1' size='340' side='right'caption='[[8dw1]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8dw1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Moloney_murine_leukemia_virus Moloney murine leukemia virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DW1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.849Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dw1 OCA], [https://pdbe.org/8dw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dw1 RCSB], [https://www.ebi.ac.uk/pdbsum/8dw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dw1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8UN00_MLVMO Q8UN00_MLVMO] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:36516684</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Georgiadis | <div class="pdbe-citations 8dw1" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Reverse transcriptase 3D structures|Reverse transcriptase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Moloney murine leukemia virus]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Georgiadis MM]] | |||