1mkl | pdb_00001mkl

NMR REFINED STRUCTURE OF THE 8,9-DIHYDRO-8-(N7-GUANYL)-9-HYDROXY-AFLATOXIN B1 ADDUCT IN A 5'-CPAFBG-3' SEQUENCE

spinqualitylabelsall models 1mkl, 1 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1mkl is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AFN Related: 1mk6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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]. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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