4HQI

Structure of O6-Benzyl-2'-deoxyguanosine opposite perimidinone-derived synthetic nucleoside in DNA duplex

Summary for 4HQI

• Entry DOI: 10.2210/pdb4hqi/pdb
• Descriptor: Short modified nucleic acids, SPERMINE, STRONTIUM ION, ... (4 entities in total)
• Functional Keywords: b-form dna, o6-benzyl-2'-deoxyguanosine, dper, perimidinone-derived nucleoside, dickerson-drew dodecamer, dna
• Biological source: SYNTHETIC CONSTRUCT
• Total number of polymer chains: 2
• Total formula weight: 7943.17

Authors

Kowal, E.A.,Lad, R.,Pallan, P.S.,Muffly, E.,Wawrzak, Z.,Egli, M.,Sturla, S.J.,Stone, M.P. (deposition date: 2012-10-25, release date: 2013-07-10, Last modification date: 2024-02-28)

Primary citation

Kowal, E.A.,Lad, R.R.,Pallan, P.S.,Dhummakupt, E.,Wawrzak, Z.,Egli, M.,Sturla, S.J.,Stone, M.P.
Recognition of O6-benzyl-2'-deoxyguanosine by a perimidinone-derived synthetic nucleoside: a DNA interstrand stacking interaction.
Nucleic Acids Res., 41:7566-7576, 2013

PubMed Abstract: The 2'-deoxynucleoside containing the synthetic base 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1H-perimidin-2(3H)-one] (dPer) recognizes in DNA the O(6)-benzyl-2'-deoxyguanosine nucleoside (O(6)-Bn-dG), formed by exposure to N-benzylmethylnitrosamine. Herein, we show how dPer distinguishes between O(6)-Bn-dG and dG in DNA. The structure of the modified Dickerson-Drew dodecamer (DDD) in which guanine at position G(4) has been replaced by O(6)-Bn-dG and cytosine C(9) has been replaced with dPer to form the modified O(6)-Bn-dG:dPer (DDD-XY) duplex [5'-d(C(1)G(2)C(3)X(4)A(5)A(6)T(7)T(8)Y(9)G(10)C(11)G(12))-3']2 (X = O(6)-Bn-dG, Y = dPer) reveals that dPer intercalates into the duplex and adopts the syn conformation about the glycosyl bond. This provides a binding pocket that allows the benzyl group of O(6)-Bn-dG to intercalate between Per and thymine of the 3'-neighbor A:T base pair. Nuclear magnetic resonance data suggest that a similar intercalative recognition mechanism applies in this sequence in solution. However, in solution, the benzyl ring of O(6)-Bn-dG undergoes rotation on the nuclear magnetic resonance time scale. In contrast, the structure of the modified DDD in which cytosine at position C(9) is replaced with dPer to form the dG:dPer (DDD-GY) [5'-d(C(1)G(2)C(3)G(4)A(5)A(6)T(7)T(8)Y(9)G(10)C(11)G(12))-3']2 duplex (Y = dPer) reveals that dPer adopts the anti conformation about the glycosyl bond and forms a less stable wobble pairing interaction with guanine.

PubMed: 23748954
DOI: 10.1093/nar/gkt488

Experimental method

X-RAY DIFFRACTION (1.7 Å)