4XPE

Crystal structure of 5'-CTTATGGGCCCATAAG in a host-guest complex

Summary for 4XPE

• Entry DOI: 10.2210/pdb4xpe/pdb
• Related: 4XNO 4XO0 4XPC
• Descriptor: reverse transcriptase, DNA (5'-D(*CP*TP*TP*AP*TP*GP*GP*G)-3'), DNA (5'-D(P*CP*CP*CP*AP*TP*AP*AP*G)-3'), ... (5 entities in total)
• Functional Keywords: host-guest complex, b-dna, non-natural nucleobase pair, synthetic biology, transferase-dna complex, transferase/dna
• Biological source: Moloney murine leukemia virus (isolate Shinnick) (MoMLV); More
• Total number of polymer chains: 3
• Total formula weight: 34325.12

Authors

Georgiadis, M.M.,Singh, I. (deposition date: 2015-01-16, release date: 2015-05-27, Last modification date: 2024-02-28)

Primary citation

Georgiadis, M.M.,Singh, I.,Kellett, W.F.,Hoshika, S.,Benner, S.A.,Richards, N.G.
Structural basis for a six nucleotide genetic alphabet.
J. Am. Chem. Soc., 137:6947-6955, 2015

PubMed Abstract: Expanded genetic systems are most likely to work with natural enzymes if the added nucleotides pair with geometries that are similar to those displayed by standard duplex DNA. Here, we present crystal structures of 16-mer duplexes showing this to be the case with two nonstandard nucleobases (Z, 6-amino-5-nitro-2(1H)-pyridone and P, 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one) that were designed to form a Z:P pair with a standard "edge on" Watson-Crick geometry, but joined by rearranged hydrogen bond donor and acceptor groups. One duplex, with four Z:P pairs, was crystallized with a reverse transcriptase host and adopts primarily a B-form. Another contained six consecutive Z:P pairs; it crystallized without a host in an A-form. In both structures, Z:P pairs fit canonical nucleobase hydrogen-bonding parameters and known DNA helical forms. Unique features include stacking of the nitro group on Z with the adjacent nucleobase ring in the A-form duplex. In both B- and A-duplexes, major groove widths for the Z:P pairs are approximately 1 Å wider than those of comparable G:C pairs, perhaps to accommodate the large nitro group on Z. Otherwise, ZP-rich DNA had many of the same properties as CG-rich DNA, a conclusion supported by circular dichroism studies in solution. The ability of standard duplexes to accommodate multiple and consecutive Z:P pairs is consistent with the ability of natural polymerases to biosynthesize those pairs. This, in turn, implies that the GACTZP synthetic genetic system can explore the entire expanded sequence space that additional nucleotides create, a major step forward in this area of synthetic biology.

PubMed: 25961938
DOI: 10.1021/jacs.5b03482

Experimental method

X-RAY DIFFRACTION (1.78 Å)