2LFX

Structure of the duplex when (5'S)-8,5'-cyclo-2'-deoxyguanosine is placed opposite dT

Summary for 2LFX

• Entry DOI: 10.2210/pdb2lfx/pdb
• Related: 2LFY
• NMR Information: BMRB: 17786
• Descriptor: DNA (5'-D(*GP*TP*GP*CP*(2LF)P*TP*GP*TP*TP*TP*GP*T)-3'), DNA (5'-D(*AP*CP*AP*AP*AP*CP*AP*TP*GP*CP*AP*C)-3') (2 entities in total)
• Functional Keywords: (5's)-8, 5'-cyclo-2'-deoxyguanosine, cyclopurine, cyclo-dg, dna
• Total number of polymer chains: 2
• Total formula weight: 7337.80

Authors

Huang, H.,Das, R.S.,Basu, A.,Stone, M.P. (deposition date: 2011-07-18, release date: 2012-06-27, Last modification date: 2024-05-15)

Primary citation

Huang, H.,Das, R.S.,Basu, A.K.,Stone, M.P.
Structures of (5'S)-8,5'-Cyclo-2'-deoxyguanosine Mismatched with dA or dT.
Chem.Res.Toxicol., 25:478-490, 2012

PubMed Abstract: Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, are induced in DNA by ionizing radiation. They are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. If not repaired, the S-8,5'-cyclo-2'-deoxyguanosine lesion (S-cdG) induces Pol V-dependent mutations at a frequency of 34% in Escherichia coli. Most are S-cdG → A transitions, suggesting mis-incorporation of dTTP opposite the lesion during replication bypass, although low levels of S-cdG → T transversions, arising from mis-incorporation of dATP, are also observed. We report the structures of 5'-d(GTGCXTGTTTGT)-3'·5'-d(ACAAACAYGCAC)-3', where X denotes S-cdG and Y denotes either dA or dT, corresponding to the situation following mis-insertion of either dTTP or dATP opposite the S-cdG lesion. The S-cdG·dT mismatch pair adopts a wobble base pairing. This provides a plausible rationale for the S-cdG → A transitions. The S-cdG·dA mismatch pair differs in conformation from the dG·dA mismatch pair. For the S-cdG·dA mismatch pair, both S-cdG and dA intercalate, but no hydrogen bonding is observed between S-cdG and dA. This is consistent with the lower levels of S-cdG → T transitions in E. coli.

PubMed: 22309170
DOI: 10.1021/tx2005053

Experimental method

SOLUTION NMR