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| | {{STRUCTURE_1axv| PDB=1axv | SCENE= }} | | {{STRUCTURE_1axv| PDB=1axv | SCENE= }} |
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| - | '''SOLUTION NMR STRUCTURE OF THE [BP]DA ADDUCT OPPOSITE DT IN A DNA DUPLEX, 6 STRUCTURES'''
| + | ===SOLUTION NMR STRUCTURE OF THE [BP]DA ADDUCT OPPOSITE DT IN A DNA DUPLEX, 6 STRUCTURES=== |
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| - | ==Overview==
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| - | Minor adducts, derived from the covalent binding of anti-benzo[a]pyrene-7,8-dihydroxy-9,10-epoxide to cellular DNA, may play an important role in generating mutations and initiating cancer. We have applied a combined NMR-computational approach including intensity based refinement to determine the solution structure of the minor (+)-cis-anti-[BP]dA adduct positioned opposite dT in the d(C1-T2-C3-T4-C5-[BP]A6-C7-T8-T9-C10-C11). (d(G12-G13-A14-A15-G16-T17-G18-A19-G20+ ++-A21-G22) 11-mer duplex. The BP ring system is intercalated toward the 5'-side of the [BP]dA6 lesion site without disrupting the flanking Watson-Crick dC5.dG18 and [BP]dA6.dT17 base pairs. This structure of the (+)-cis-anti-[BP]dA.dT 11-mer duplex, containing a bay region benzo[a]pyrenyl [BP]dA adduct, is compared with the corresponding structure of the (+)-trans-anti-[BPh]dA.dT 11-mer duplex (Cosman et al., Biochemistry 32, 12488-12497, 1993), which contains a fjord region benzo[c]phenanthrenyl [BPh]dA adduct with the same R stereochemistry at the linkage site. The carcinogen intercalates toward the 5'-direction of the modified strand in both duplexes (the adduct is embedded within the same sequence context) with the buckling of the Watson-Crick [BP]dA6.dT17 base pair more pronounced in the (+)-cis-anti-[BP]dA.dT 11-mer duplex compared to its Watson-Crick [BPh]dA.dT17 base pair in the (+)-trans-anti-[BPh]dA.dT 11-mer duplex. The available structural studies of covalent polycyclic aromatic hydrocarbon (PAH) carcinogen-DNA adducts point toward the emergence of a general theme where distinct alignments are adopted by PAH adducts covalently linked to the N(6) of adenine when compared to the N(2) of guanine in DNA duplexes. The [BPh]dA and [BP]dA N(6)-adenine adducts intercalate their polycyclic aromatic rings into the helix without disruption of their modified base pairs. This may reflect the potential flexibility associated with the positioning of the covalent tether and the benzylic ring of the carcinogen in the sterically spacious major groove. By contrast, such an intercalation without modified base pair disruption option appears not to be available to [BP]dG N(2)-guanine adducts where the covalent tether and the benzylic ring are positioned in the more sterically crowded minor groove. In the case of [BP]dG adducts, the benzopyrenyl ring is either positioned in the minor groove without base pair disruption, or if intercalated into the helix, requires disruption of the modified base pair and displacement of the bases out of the helix.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10451380}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10451380 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10451380}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AXV OCA]. | + | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AXV OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Carcinogen adduct]] | | [[Category: Carcinogen adduct]] |
| | [[Category: Dna duplex]] | | [[Category: Dna duplex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:49:32 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 17:49:33 2008'' |
Revision as of 14:49, 30 June 2008
Template:STRUCTURE 1axv
SOLUTION NMR STRUCTURE OF THE [BP]DA ADDUCT OPPOSITE DT IN A DNA DUPLEX, 6 STRUCTURES
Template:ABSTRACT PUBMED 10451380
About this Structure
Full experimental information is available from OCA.
Reference
Solution structure of the (+)-cis-anti-benzo[a]pyrene-dA ([BP]dA) adduct opposite dT in a DNA duplex., Mao B, Gu Z, Gorin A, Chen J, Hingerty BE, Amin S, Broyde S, Geacintov NE, Patel DJ, Biochemistry. 1999 Aug 17;38(33):10831-42. PMID:10451380
Page seeded by OCA on Mon Jun 30 17:49:33 2008
