288d
From Proteopedia
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| - | [[Image:288d.gif|left|200px]] | + | [[Image:288d.gif|left|200px]] |
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| - | '''SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY''' | + | {{Structure |
| + | |PDB= 288d |SIZE=350|CAPTION= <scene name='initialview01'>288d</scene>, resolution 1.800Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=DM8:2'-BROMO-4'-EPIDAUNORUBICIN'>DM8</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 288D is a [ | + | 288D is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=288D OCA]. |
==Reference== | ==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:// | + | 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: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Gao, Y G.]] | [[Category: Gao, Y G.]] | ||
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[[Category: right handed dna]] | [[Category: right handed dna]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:43:39 2008'' |
Revision as of 13:43, 20 March 2008
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| , resolution 1.800Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
SUBSTITUTIONS AT C2' OF DAUNOSAMINE IN THE ANTICANCER DAUNORUBICIN ALTER ITS DNA-BINDING SEQUENCE SPECIFICITY
Overview
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.
About this Structure
288D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from 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:8841395
Page seeded by OCA on Thu Mar 20 15:43:39 2008
