2oks
From Proteopedia
(New page: 200px<br /><applet load="2oks" size="350" color="white" frame="true" align="right" spinBox="true" caption="2oks, resolution 1.65Å" /> '''X-ray Structure of a...) |
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==Overview== | ==Overview== | ||
| - | Chemotherapeutic alkylating agents, such as bifunctional nitrogen mustards | + | Chemotherapeutic alkylating agents, such as bifunctional nitrogen mustards and cisplatins, generate interstrand DNA cross-links that inhibit cell proliferation by arresting DNA transcription and replication. A synthetic N4C-ethyl-N4C interstrand cross-link between opposing cytidines mimics the DNA damage produced by this class of clinically important compounds and can be synthesized in large quantities to study the repair, physical properties, and structures of these DNA adducts. The X-ray structure of a DNA duplex d(CCAAC*GTTGG)2 containing a synthetic N4C-ethyl-N4C interstrand cross-link between the cytosines of the central CpG step (*) has been determined at 1.65 A resolution. This structure reveals that the ethyl cross-link in the CpG major groove does not significantly disrupt the B-form DNA helix. Comparison of the N4C-ethyl-N4C cross-linked structure with the structure of an un-cross-linked oligonucleotide of the same sequence reveals that the cross-link selectively stabilizes a preexisting alternative conformation. The conformation preferred by the cross-linked DNA is constrained by the geometry of the ethyl group bridging the cytosine amines. Characteristics of the cross-linked CpG step include subtle differences in the roll of the base pairs, optimized Watson-Crick hydrogen bonds, and loss of a divalent cation binding site. Given that the N4C-ethyl-N4C cross-link stabilizes a preexisting conformation of the CpG step, this synthetically accessible substrate presents an ideal model system for studying the genomic effects of covalently coupling the DNA strands, independent of gross alterations in DNA structure. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Structure of a DNA repair substrate containing an alkyl interstrand cross-link at 1.65 | + | Structure of a DNA repair substrate containing an alkyl interstrand cross-link at 1.65 A resolution., Swenson MC, Paranawithana SR, Miller PS, Kielkopf CL, Biochemistry. 2007 Apr 17;46(15):4545-53. Epub 2007 Mar 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17375936 17375936] |
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Kielkopf, C | + | [[Category: Kielkopf, C L.]] |
| - | [[Category: Miller, P | + | [[Category: Miller, P S.]] |
| - | [[Category: Paranawithana, S | + | [[Category: Paranawithana, S R.]] |
| - | [[Category: Swenson, M | + | [[Category: Swenson, M C.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: EHN]] | [[Category: EHN]] | ||
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[[Category: interstrand crosslink]] | [[Category: interstrand crosslink]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:19:38 2008'' |
Revision as of 16:19, 21 February 2008
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X-ray Structure of a DNA Repair Substrate Containing an Alkyl Interstrand Crosslink at 1.65 Resolution
Overview
Chemotherapeutic alkylating agents, such as bifunctional nitrogen mustards and cisplatins, generate interstrand DNA cross-links that inhibit cell proliferation by arresting DNA transcription and replication. A synthetic N4C-ethyl-N4C interstrand cross-link between opposing cytidines mimics the DNA damage produced by this class of clinically important compounds and can be synthesized in large quantities to study the repair, physical properties, and structures of these DNA adducts. The X-ray structure of a DNA duplex d(CCAAC*GTTGG)2 containing a synthetic N4C-ethyl-N4C interstrand cross-link between the cytosines of the central CpG step (*) has been determined at 1.65 A resolution. This structure reveals that the ethyl cross-link in the CpG major groove does not significantly disrupt the B-form DNA helix. Comparison of the N4C-ethyl-N4C cross-linked structure with the structure of an un-cross-linked oligonucleotide of the same sequence reveals that the cross-link selectively stabilizes a preexisting alternative conformation. The conformation preferred by the cross-linked DNA is constrained by the geometry of the ethyl group bridging the cytosine amines. Characteristics of the cross-linked CpG step include subtle differences in the roll of the base pairs, optimized Watson-Crick hydrogen bonds, and loss of a divalent cation binding site. Given that the N4C-ethyl-N4C cross-link stabilizes a preexisting conformation of the CpG step, this synthetically accessible substrate presents an ideal model system for studying the genomic effects of covalently coupling the DNA strands, independent of gross alterations in DNA structure.
About this Structure
2OKS is a Protein complex structure of sequences from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
Structure of a DNA repair substrate containing an alkyl interstrand cross-link at 1.65 A resolution., Swenson MC, Paranawithana SR, Miller PS, Kielkopf CL, Biochemistry. 2007 Apr 17;46(15):4545-53. Epub 2007 Mar 22. PMID:17375936
Page seeded by OCA on Thu Feb 21 18:19:38 2008
