2pis

From Proteopedia

---

Revision as of 10:37, 23 January 2008

proteopedia linkproteopedia link

spinqualitylabelsall models 2pis, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Efforts toward Expansion of the Genetic Alphabet: Structure and Replication of Unnatural Base Pairs

Overview

Expansion of the genetic alphabet has been a long-time goal of chemical, biology. A third DNA base pair that is stable and replicable would have a, great number of practical applications and would also lay the foundation, for a semisynthetic organism. We have reported that DNA base pairs formed, between deoxyribonucleotides with large aromatic, predominantly, hydrophobic nucleobase analogues, such as propynylisocarbostyril (dPICS), are stable and efficiently synthesized by DNA polymerases. However, once, incorporated into the primer, these analogues inhibit continued primer, elongation. More recently, we have found that DNA base pairs formed, between nucleobase analogues that have minimal aromatic surface area in, addition to little or no hydrogen-bonding potential, such as, 3-fluorobenzene (d3FB), are synthesized and extended by DNA polymerases, with greatly increased efficiency. Here we show that the rate of synthesis, and extension of the self-pair formed between two d3FB analogues is, sufficient for in vitro DNA replication. To better understand the origins, of efficient replication, we examined the structure of DNA duplexes, containing either the d3FB or dPICS self-pairs. We find that the large, aromatic rings of dPICS pair in an intercalative manner within duplex DNA, while the d3FB nucleobases interact in an edge-on manner, much closer in, structure to natural base pairs. We also synthesized duplexes containing, the 5-methyl-substituted derivatives of d3FB (d5Me3FB) paired opposite, d3FB or the unsubstituted analogue (dBEN). In all, the data suggest that, the structure, electrostatics, and dynamics can all contribute to the, extension of unnatural primer termini. The results also help explain the, replication properties of many previously examined unnatural base pairs, and should help design unnatural base pairs that are better replicated.

About this Structure

2PIS is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.

Reference

Efforts toward expansion of the genetic alphabet: structure and replication of unnatural base pairs., Matsuda S, Fillo JD, Henry AA, Rai P, Wilkens SJ, Dwyer TJ, Geierstanger BH, Wemmer DE, Schultz PG, Spraggon G, Romesberg FE, J Am Chem Soc. 2007 Aug 29;129(34):10466-73. Epub 2007 Aug 8. PMID:17685517

Page seeded by OCA on Wed Jan 23 12:37:01 2008