1n4b
From Proteopedia
(New page: 200px<br /><applet load="1n4b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n4b" /> '''Solution Structure of the undecamer CGAAAC*T...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1n4b.gif|left|200px]]<br /><applet load="1n4b" size=" | + | [[Image:1n4b.gif|left|200px]]<br /><applet load="1n4b" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1n4b" /> | caption="1n4b" /> | ||
'''Solution Structure of the undecamer CGAAAC*TTTCG'''<br /> | '''Solution Structure of the undecamer CGAAAC*TTTCG'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The solution structure of an interstrand cross-linked self-complementary | + | The solution structure of an interstrand cross-linked self-complementary oligodeoxynucleotide containing directly opposed alkylated N(4)C-ethyl-N(4)C cytosine bases was determined by molecular dynamics calculations guided by NMR-derived restraints. The undecamer d(CGAAACTTTCG)(2), where C represents directly opposed alkylated N(4)C-ethyl-N(4)C cytosine bases, serves as model for the cytotoxic cross-links formed by bifunctional alkylating agents used in cancer therapy. The structure of the duplex shows the cross-link protruding into the major groove. An increase in the diameter of the DNA at the pseudoplatform formed by the cross-linked residues creates an A-DNA characteristic hole in the central portion of the DNA. This results in a centrally underwound base step and a number of subsequent overwinding steps leading to an overall axis bend toward the major groove. The structure shows narrowing of both minor and major grooves in the proximity of the cross-link. The perturbation leads to preferential intrastrand base stacking, disruption of adjacent canonical (A.T) base pairing, and buckling of base pairs, the extent of which diminishes with progression away from the lesion site. Overall, the distortion induced by the cross-link spreads over three base pairs on the 5'- and 3'-sides of the cross-link. |
==About this Structure== | ==About this Structure== | ||
| - | 1N4B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with EHN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1N4B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=EHN:'>EHN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N4B OCA]. |
==Reference== | ==Reference== | ||
Solution structure of a DNA duplex containing mispair-aligned N4C-ethyl-N4C interstrand cross-linked cytosines., Webba da Silva M, Noronha AM, Noll DM, Miller PS, Colvin OM, Gamcsik MP, Biochemistry. 2002 Dec 24;41(51):15181-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12484755 12484755] | Solution structure of a DNA duplex containing mispair-aligned N4C-ethyl-N4C interstrand cross-linked cytosines., Webba da Silva M, Noronha AM, Noll DM, Miller PS, Colvin OM, Gamcsik MP, Biochemistry. 2002 Dec 24;41(51):15181-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12484755 12484755] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Colvin, O | + | [[Category: Colvin, O M.]] |
| - | [[Category: Gamcsik, M | + | [[Category: Gamcsik, M P.]] |
| - | [[Category: Miller, P | + | [[Category: Miller, P S.]] |
| - | [[Category: Noll, D | + | [[Category: Noll, D M.]] |
| - | [[Category: Noronha, A | + | [[Category: Noronha, A M.]] |
| - | [[Category: Silva, M | + | [[Category: Silva, M Webba da.]] |
[[Category: EHN]] | [[Category: EHN]] | ||
[[Category: alkylated cytosine]] | [[Category: alkylated cytosine]] | ||
| Line 24: | Line 24: | ||
[[Category: modified cytosine]] | [[Category: modified cytosine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:05 2008'' |
Revision as of 12:02, 21 February 2008
|
Solution Structure of the undecamer CGAAAC*TTTCG
Overview
The solution structure of an interstrand cross-linked self-complementary oligodeoxynucleotide containing directly opposed alkylated N(4)C-ethyl-N(4)C cytosine bases was determined by molecular dynamics calculations guided by NMR-derived restraints. The undecamer d(CGAAACTTTCG)(2), where C represents directly opposed alkylated N(4)C-ethyl-N(4)C cytosine bases, serves as model for the cytotoxic cross-links formed by bifunctional alkylating agents used in cancer therapy. The structure of the duplex shows the cross-link protruding into the major groove. An increase in the diameter of the DNA at the pseudoplatform formed by the cross-linked residues creates an A-DNA characteristic hole in the central portion of the DNA. This results in a centrally underwound base step and a number of subsequent overwinding steps leading to an overall axis bend toward the major groove. The structure shows narrowing of both minor and major grooves in the proximity of the cross-link. The perturbation leads to preferential intrastrand base stacking, disruption of adjacent canonical (A.T) base pairing, and buckling of base pairs, the extent of which diminishes with progression away from the lesion site. Overall, the distortion induced by the cross-link spreads over three base pairs on the 5'- and 3'-sides of the cross-link.
About this Structure
1N4B is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Solution structure of a DNA duplex containing mispair-aligned N4C-ethyl-N4C interstrand cross-linked cytosines., Webba da Silva M, Noronha AM, Noll DM, Miller PS, Colvin OM, Gamcsik MP, Biochemistry. 2002 Dec 24;41(51):15181-8. PMID:12484755
Page seeded by OCA on Thu Feb 21 14:02:05 2008
