5W20

Crystal Structure of inosine-substituted duplex DNA

Summary for 5W20

• Entry DOI: 10.2210/pdb5w20/pdb
• Related: 5W1Z
• Descriptor: DNA (5'-D(*CP*CP*AP*IP*IP*CP*CP*TP*GP*G)-3'), MAGNESIUM ION (3 entities in total)
• Functional Keywords: inosine, dna crystal structure, deoxyinonsine, circular dichroism of modified dna, dna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 6177.76

Authors

Pallan, P.S.,Egli, M. (deposition date: 2017-06-05, release date: 2017-08-23, Last modification date: 2024-03-13)

Primary citation

Peters, J.P.,Kowal, E.A.,Pallan, P.S.,Egli, M.,Maher 3rd., L.J.
Comparative analysis of inosine-substituted duplex DNA by circular dichroism and X-ray crystallography.
J. Biomol. Struct. Dyn., 36:2753-2772, 2018

PubMed Abstract: Leveraging structural biology tools, we report the results of experiments seeking to determine if the different mechanical properties of DNA polymers with base analog substitutions can be attributed, at least in part, to induced changes from classical B-form DNA. The underlying hypothesis is that different inherent bending and twisting flexibilities may characterize non-canonical B-DNA, so that it is inappropriate to interpret mechanical changes caused by base analog substitution as resulting simply from 'electrostatic' or 'base stacking' influences without considering the larger context of altered helical geometry. Circular dichroism spectra of inosine-substituted oligonucleotides and longer base-substituted DNAs in solution indicated non-canonical helical conformations, with the degree of deviation from a standard B-form geometry depending on the number of I⋅C pairs. X-ray diffraction of a highly inosine-substituted DNA decamer crystal (eight I⋅C and two A⋅T pairs) revealed an A-tract-like conformation with a uniformly narrow minor groove, reduced helical rise, and the majority of sugars adopting a C1'-exo (southeastern) conformation. This contrasts with the standard B-DNA geometry with C2'-endo sugar puckers (south conformation). In contrast, the crystal structure of a decamer with only four I⋅C pairs has a geometry similar to that of the reference duplex with eight G⋅C and two A⋅T pairs. The unique crystal geometry of the inosine-rich duplex is noteworthy given its unusual CD signature in solution and the altered mechanical properties of some inosine-containing DNAs.

PubMed: 28818035
DOI: 10.1080/07391102.2017.1369164

Experimental method

X-RAY DIFFRACTION (1.36 Å)