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4RHD

DNA Duplex with Novel ZP Base Pair

Summary for 4RHD
Entry DOI10.2210/pdb4rhd/pdb
DescriptorDNA 9mer novel Z nucleobase, DNA 9mer novel P nucleobase, MAGNESIUM ION, ... (4 entities in total)
Functional Keywordsmodified nucleobase z and p, dna
Biological sourcesynthetic construct
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Total number of polymer chains8
Total formula weight22750.88
Authors
Zhang, W.,Zhang, L.,Benner, S.,Huang, Z. (deposition date: 2014-10-01, release date: 2015-07-08, Last modification date: 2024-02-28)
Primary citationZhang, L.,Yang, Z.,Sefah, K.,Bradley, K.M.,Hoshika, S.,Kim, M.J.,Kim, H.J.,Zhu, G.,Jimenez, E.,Cansiz, S.,Teng, I.T.,Champanhac, C.,McLendon, C.,Liu, C.,Zhang, W.,Gerloff, D.L.,Huang, Z.,Tan, W.,Benner, S.A.
Evolution of functional six-nucleotide DNA.
J.Am.Chem.Soc., 137:6734-6737, 2015
Cited by
PubMed Abstract: Axiomatically, the density of information stored in DNA, with just four nucleotides (GACT), is higher than in a binary code, but less than it might be if synthetic biologists succeed in adding independently replicating nucleotides to genetic systems. Such addition could also add functional groups not found in natural DNA, but useful for molecular performance. Here, we consider two new nucleotides (Z and P, 6-amino-5-nitro-3-(1'-β-D-2'-deoxyribo-furanosyl)-2(1H)-pyridone and 2-amino-8-(1'-β-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one). These are designed to pair via complete Watson-Crick geometry. These were added to a library of oligonucleotides used in a laboratory in vitro evolution (LIVE) experiment; the GACTZP library was challenged to deliver molecules that bind selectively to liver cancer cells, but not to untransformed liver cells. Unlike in classical in vitro selection, low levels of mutation allow this system to evolve to create binding molecules not necessarily present in the original library. Over a dozen binding species were recovered. The best had Z and/or P in their sequences. Several had multiple, nearby, and adjacent Zs and Ps. Only the weaker binders contained no Z or P at all. This suggests that this system explored much of the sequence space available to this genetic system and that GACTZP libraries are richer reservoirs of functionality than standard libraries.
PubMed: 25966323
DOI: 10.1021/jacs.5b02251
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.7 Å)
Structure validation

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