2pis
From Proteopedia
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[[Image:2pis.gif|left|200px]] | [[Image:2pis.gif|left|200px]] | ||
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'''Efforts toward Expansion of the Genetic Alphabet: Structure and Replication of Unnatural Base Pairs''' | '''Efforts toward Expansion of the Genetic Alphabet: Structure and Replication of Unnatural Base Pairs''' | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2PIS is a [[Single protein]] structure | + | 2PIS is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Wemmer, D E.]] | [[Category: Wemmer, D E.]] | ||
[[Category: Wilkins, S J.]] | [[Category: Wilkins, S J.]] | ||
| - | [[Category: | + | [[Category: Dna]] |
| - | [[Category: | + | [[Category: Duplex]] |
| - | [[Category: | + | [[Category: Nucleic acid]] |
| - | [[Category: | + | [[Category: Replication]] |
| - | [[Category: | + | [[Category: Unnatural base]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:11:57 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:11, 4 May 2008
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. 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 Sun May 4 13:11:57 2008
