5w20

Publication Abstract from PubMed

Leveraging structural biology tools, we report the results of experimentsseeking 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 dichroismspectra 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 IC pairs.X-ray diffraction of a highly inosine-substituted DNA decamer crystal (eight IC and two AT pairs)revealedan 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 adecamer with only four IC pairs has a geometry similar to that of the reference duplex with eight GC and two AT pairs.The unique crystal geometry of the inosine-rich duplex is noteworthy given its unusual CD signaturein solution and the altered mechanical properties of someinosine-containing DNAs.

Comparative analysis of inosine-substituted duplex DNA by circular dichroism and X-ray crystallography.,Peters JP, Kowal EA, Pallan PS, Egli M, Maher LJ 3rd J Biomol Struct Dyn. 2017 Aug 18:1-60. doi: 10.1080/07391102.2017.1369164. PMID:28818035^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.