Acta Crystallographica Section D: Structural Biology
Acta Crystallographica Section D: Structural Biology
5 years ago

Mismodeled purines: implicit alternates and hidden Hoogsteens

Mismodeled purines: implicit alternates and hidden Hoogsteens
David C. Richardson, Jane S. Richardson, Bradley J. Hintze
Hoogsteen base pairs are seen in DNA crystal structures, but only rarely. This study tests whether Hoogsteens or other syn purines are either under-modeled or over-modeled, which are known problems for rare conformations. Candidate purines needing a syn/anti 180° flip were identified by diagnostic patterns of difference electron-density peaks. Manual inspection narrowed 105 flip candidates to 20 convincing cases, all at ≤2.7 Å resolution. Rebuilding and refinement confirmed that 14 of these were authentic purine flips. Seven examples are modeled as Watson–Crick base pairs but should be Hoogsteens (commonest at duplex termini), and three had the opposite issue. Syn/anti flips were also needed for some single-stranded purines. Five of the 20 convincing cases arose from an unmodeled alternate duplex running in the opposite direction. These are in semi-palindromic DNA sequences bound by a homodimeric protein and show flipped-purine-like difference peaks at residues where the palindrome is imperfect. This study documents types of incorrect modeling which are worth avoiding. However, the primary conclusions are that such mistakes are infrequent, the bias towards fitting anti purines is very slight, and the occurrence rate of Hoogsteen base pairs in DNA crystal structures remains unchanged from earlier estimates at ∼0.3%.This paper describes a method that employs difference electron density to identify DNA purines modeled in the incorrect syn/anti conformation. Different classes of mistakes that were identified by using this method to survey all PDB models containing DNA are highlighted.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1107/S2059798317013729

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