1amd: Difference between revisions
From Proteopedia
Jump to navigationJump to search
m Protected "1amd" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
[[ | ==NMR STUDY OF DNA (5'-D(*TP*GP*TP*AP*CP*A)-3') SELF-COMPLEMENTARY DUPLEX COMPLEXED WITH A BIS-DAUNORUBICIN WP-652, MINIMIZED AVERAGE STRUCTURE== | ||
<StructureSection load='1amd' size='340' side='right' caption='[[1amd]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1amd]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AMD FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BNR:BIS-DAUNORUBICIN'>BNR</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1al9|1al9]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1amd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1amd RCSB], [http://www.ebi.ac.uk/pdbsum/1amd PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In the search for new generations of anthracycline drugs, lower cytotoxic side effects and higher activity against resistant cancer cells are two major goals. A new class of bis-intercalating anthracycline drugs has been designed, synthesized, and shown to have promising activity against multidrug-resistant cells. Two daunorubicins symmetrically linked together via a p-xylenyl group, either at their N3' (compound WP631) or N4' sites (compound WP652), exhibit extraordinary DNA binding affinities. We have used high-resolution NRM studies to understand the DNA binding mode of these two new bis-daunorubicin anticancer compounds. The structures of the WP631-d(ACGTACGT)2 and the WP652-d(TGTACA)2 complexes have been determined by NOE-restrained refinement. WP631 binds strongly to the 5'-CG(A/T)(A/T)CG hexanucleotide sequence, with the aglycons intercalated between the two CpG sites at both ends of the hexanucleotide sequence. The overall conformation of the WP631-d(CGTACG)2 part is remarkably similar to the crystal structure of the 2:1 complex of daunorubicin and d(CGTACG)2, as predicted previously [Gao, Y.-G., & Wang, A.H.H. (1996), J. Biomol. Struct. Dyn. 13, 103-117]. In contrast, the related bis-intercalator WP652 prefers the 5'-PyGTPu tetranucleotide sequence, with the aglycons intercalated between the PypG and TpPu sites. The binding of WP652 to DNA results in a severely distroted B-DNA duplex with the p-xylenyl tether moiety significantly protruded away from the bottom of the minor groove. While WP652 in some ways behaves similarly to other anticancer bis-intercalating antibiotics (e.g., triostine A and echinomycin), the detailed interactions between those two classes of bis-intercalators are quite different. | |||
Binding of two novel bisdaunorubicins to DNA studied by NMR spectroscopy.,Robinson H, Priebe W, Chaires JB, Wang AH Biochemistry. 1997 Jul 22;36(29):8663-70. PMID:9289011<ref>PMID:9289011</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Robinson, H.]] | [[Category: Robinson, H.]] | ||
[[Category: Wang, A H.J.]] | [[Category: Wang, A H.J.]] | ||
