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| - | [[Image:278d.gif|left|200px]] | |
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| - | <!--
| + | ==SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY== |
| - | The line below this paragraph, containing "STRUCTURE_278d", creates the "Structure Box" on the page.
| + | <StructureSection load='278d' size='340' side='right'caption='[[278d]], [[Resolution|resolution]] 1.80Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[278d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=278D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=278D FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | -->
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DM8:2-BROMO-4-EPIDAUNORUBICIN'>DM8</scene>, <scene name='pdbligand=G49:N2-METHYL-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>G49</scene></td></tr> |
| - | {{STRUCTURE_278d| PDB=278d | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=278d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=278d OCA], [https://pdbe.org/278d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=278d RCSB], [https://www.ebi.ac.uk/pdbsum/278d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=278d ProSAT]</span></td></tr> |
| - | | + | </table> |
| - | '''SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY'''
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | | + | [[Category: Large Structures]] |
| - | ==Overview== | + | [[Category: Gao Y-G]] |
| - | In the search for new generations of anthracycline drugs, lower cytotoxic side effect and higher activity toward resistant cancer cells are two major goals. A new anthracycline drug, WP401 (2'-bromo-4'-epidaunorubicin, alpha-manno configuration), exhibits promising activity toward multidrug-resistant cells. In contrast, the related compound WP400 (2'-bromo-4'-epidaunorubicin, alpha-gluco configuration), is significantly less cytotoxic. To establish the structural and molecular bases of this observation, we performed X-ray diffraction analyses of the complexes between WP401 and four DNA hexamers CGTACG, CGATCG, CGCGCG, and CGGCCG. Their crystal data (space group P4(1)2(1)2, a = b approximately 2.8 nm, c approximately 5.3 nm) are similar to those of other daunorubicin/doxorubicin complexes. The refined crystal structures at 0.18-nm resolution revealed that two WP401 drug molecules bind to the duplex, with the aglycons intercalated between the CpG steps and their modified daunosamines in the minor groove. The bulky bromine atom at the C2' position caused the daunosamine of the bound WP401 to adopt a different conformation from that of the bound daunorubicin. In the presence of formaldehyde, WP401 formed a covalent adduct with CGGCCG more readily than with CGCGCG. This is the opposite of what is seen for daunorubicin and doxorubicin. Thus modifications at the C2' position of daunosamine modulate the sequence specificity of the formaldehyde-crosslinking reactions between anthracyclines and DNA.
| + | [[Category: Priebe W]] |
| - | | + | [[Category: Wang AH-J]] |
| - | ==About this Structure== | + | |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=278D OCA]. | + | |
| - | | + | |
| - | ==Reference== | + | |
| - | Substitutions at C2' of daunosamine in the anticancer drug daunorubicin alter its DNA-binding sequence specificity., Gao YG, Priebe W, Wang AH, Eur J Biochem. 1996 Sep 1;240(2):331-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8841395 8841395]
| + | |
| - | [[Category: Gao, Y G.]]
| + | |
| - | [[Category: Priebe, W.]]
| + | |
| - | [[Category: Wang, A H.J.]] | + | |
| - | [[Category: Complexed with drug]] | + | |
| - | [[Category: Double helix]] | + | |
| - | [[Category: Modified]] | + | |
| - | [[Category: Right handed dna]] | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:25:07 2008''
| + | |
