3HGD: Crystal Structure of 2-Se-Thymidine Derivatized DNA

The base pairs are the contributors to the sequence-dependent recognition of nucleic acids, genetic information storage, and high fidelity of DNA polymerase replication. However, the wobble base pairing, where T pairs with G instead of A, reduces specific base-pairing recognition and compromises the high fidelity of the enzymatic polymerization. Via the selenium atomic probing at the 2-position of thymidine, we have investigated the wobble discrimination by manipulating the steric and electronic effects at the 2-exo position, providing a unique chemical strategy to enhance the base pair specificity. We report here the first synthesis of the novel 2-Se-thymidine ((Se)T) derivative, its phosphoramidite, and the Se-DNAs. Our biophysical and structural studies of the 2-Se-T DNAs reveal that the bulky 2-Se atom with a weak hydrogen-bonding ability can largely increase mismatch discriminations (including T/G wobble and T/C mismatched base pairs) while maintaining the (Se)T/A virtually identical to the native T/A base pair. The 2-Se atom bulkiness and the electronic effect are probably the main factors responsible for the discrimination against the formation of the wobble (Se)T/G base pair. Our investigations provide a potential novel tool to investigate the specific recognition of base pairs, which is the basis of high fidelity during replication, transcription, and translation. Furthermore, this Se-atom-specific substitution and probing are useful for X-ray crystal structure and function studies of nucleic acids.
PDB ID: 3HGDDownload
MMDB ID: 76106
PDB Deposition Date: 2009/5/13
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.57  Å
Biological Unit for 3HGD: dimeric; determined by author and by software (PISA)
Molecular Components in 3HGD
Label Count Molecule
Nucleotide(1 molecule)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB