1mkl
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(New page: 200px<br /><applet load="1mkl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mkl" /> '''NMR REFINED STRUCTURE OF THE 8,9-DIHYDRO-8-(...)
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Revision as of 02:10, 25 November 2007
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NMR REFINED STRUCTURE OF THE 8,9-DIHYDRO-8-(N7-GUANYL)-9-HYDROXY-AFLATOXIN B1 ADDUCT IN A 5'-CPAFBG-3' SEQUENCE
Overview
The structure of the cationic, 8,9-dihydro-8-(N7-guanyl)-9-hydroxy-aflatoxin B(1) adduct embedded in a, 5'-CpG-3' sequence context and paired with deoxycytosine in the, oligodeoxynucleotide d(ACATC(AFB)GATCT) x d(AGATCGATGT) was refined using, molecular dynamics calculations restrained by NOE data and dihedral angle, restraints obtained from NMR data. The aflatoxin moiety intercalated above, the 5' face of the modified guanine. It stacked between C(5) x G(16) and, (AFB)G(6) x C(15). The AFB(1) H5, OCH(3), and methylene protons faced into, the minor groove, with the methylene protons oriented between the C(15), and G(16) nucleobases. The aflatoxin B(1) H6a, H8, H9, and H9a protons, faced the major groove, with H6a and H9a pointing toward the 5' direction, from the lesion site. The refined structure was compared to the structure, of the aflatoxin B(1) adduct embedded in a 5'-ATGCAT-3' sequence in the, oligodeoxynucleotide d(TAT(AFB)GCATA)(2) [Jones, W. R., Johnston, D. S., and Stone, M. P. (1998) Chem. Res. Toxicol.11, 873-881]. The structure of, the intercalated aflatoxin B(1) lesion in the ATC(AFB)GAT sequence is, similar to its structure in the d(AT(AFB)GCAT) sequence. This is, consistent with a mechanism in which the precovalent intercalation of, aflatoxin-8,9-exo-epoxide on the 5' face of guanine places the epoxide in, close proximity and in the proper orientation to the N7 position of, guanine, thus facilitating an S(N)2 reaction. The data provides additional, insight into the nature of the disruption of the B-DNA duplex induced by, aflatoxin B(1) intercalation. Overall, the results suggest that sequence, contributes a minor role in modulating the structure of the cationic, guanine N7 AFB(1) lesion in duplex DNA. On the other hand, structural, differences are observed when the correctly paired structure is compared, to the structure of the cationic AFB(1) adduct mispaired with dA [Giri, I., Johnston, D. S., and Stone, M. P. (2002) Biochemistry 41, 5462-5472].
About this Structure
1MKL is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Structural refinement of the 8,9-dihydro-8-(N7-guanyl)-9-hydroxy-aflatoxin B(1) adduct in a 5'-Cp(AFB)G-3' sequence., Giri I, Jenkins MD, Schnetz-Boutaud NC, Stone MP, Chem Res Toxicol. 2002 May;15(5):638-47. PMID:12018984
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