1mxj
From Proteopedia
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NMR solution structure of benz[a]anthracene-dG in ras codon 12,2; GGCAGXTGGTG
Overview
The conformation of the, trans-anti-(1S,2R,3S,4R)-N(2)-[1-(1,2,3,4-tetrahydro-2,3,4-trihydroxybenz[, a]anthracenyl)]-2'-deoxyguanosyl adduct in, d(G(1)G(2)C(3)A(4)G(5)X(6)T(7)G(8)G(9)T(10)G(11)).d(C(12)A(13)C(14)C(15)A(, 16)C(17)C(18)T(19)G(20)C(21)C(22)), bearing codon 12 of the human N-ras, protooncogene (underlined), was determined. This adduct had S, stereochemistry at the benzylic carbon. Its occurrence in DNA is a, consequence of trans opening by the deoxyguanosine amino group of, (1R,2S,3S,4R)-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracenyl-3,4-diol. The, resonance frequencies, relative to the unmodified DNA, of the X(6) H1' and, H6 protons were shifted downfield, whereas those of the C(18) and T(19), H1', H2', H2' ', and H3' deoxyribose protons were shifted upfield. The, imino and amino resonances exhibited the expected sequential, connectivities, suggesting no interruption of Watson-Crick pairing. A, total of 426 interproton distances, including nine uniquely assigned, BA-DNA distances, were used in the restrained molecular dynamics, calculations. The refined structure showed that the benz[a]anthracene, moiety bound in the minor groove, in the 5'-direction from the modified, site. This was similar to the (+)-trans-anti-benzo[a]pyrene-N(2)-dG adduct, having S stereochemistry at the benzylic carbon [Cosman, M., De Los, Santos, C., Fiala, R., Hingerty, B. E., Singh, S. B., Ibanez, V., Margulis, L. A., Live, D., Geacintov, N. E., Broyde, S., and Patel, D. J., (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918]. It differed from the, (-)-trans-anti-benzo[c]phenanthrene-N(2)-dG adduct having S, stereochemistry at the benzylic carbon, which intercalated in the, 5'-direction [Lin, C. H., Huang, X., Kolbanovskii, A., Hingerty, B. E., Amin, S., Broyde, S., Geacintov, N. E., and Patel, D. J. (2001) J. Mol., Biol. 306, 1059-1080]. The results provided insight into how PAH molecular, topology modulates adduct structure in duplex DNA.
About this Structure
1MXJ is a Protein complex structure of sequences from [1] with BZR as ligand. Full crystallographic information is available from OCA.
Reference
Minor groove orientation for the (1S,2R,3S,4R)-N2- [1-(1,2,3,4-tetrahydro-2,3,4-trihydroxybenz[a]anthracenyl)]-2'-deoxyguanos yl adduct in the N-ras codon 12 sequence., Kim HY, Wilkinson AS, Harris CM, Harris TM, Stone MP, Biochemistry. 2003 Mar 4;42(8):2328-38. PMID:12600200
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