3HGD

Crystal Structure of 2-Se-Thymidine Derivatized DNA

Summary for 3HGD

• Entry DOI: 10.2210/pdb3hgd/pdb
• Related: 3HG8 3HGA
• Descriptor: 5'-D(*GP*(UMS)P*GP*(US3)P*AP*CP*AP*C)-3' (2 entities in total)
• Functional Keywords: 2-se-thymidine dna, dna
• Total number of polymer chains: 2
• Total formula weight: 5137.08

Authors

Sheng, J.,Hassan, A.E.,Zhang, W.,Huang, Z. (deposition date: 2009-05-13, release date: 2009-08-18, Last modification date: 2024-02-21)

Primary citation

Hassan, A.E.,Sheng, J.,Zhang, W.,Huang, Z.
High fidelity of base pairing by 2-selenothymidine in DNA.
J.Am.Chem.Soc., 132:2120-2121, 2010

PubMed Abstract: 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.

PubMed: 20108896
DOI: 10.1021/ja909330m

Experimental method

X-RAY DIFFRACTION (1.57 Å)