7RSU

TNA polymerase, n+2 product

Summary for 7RSU

• Entry DOI: 10.2210/pdb7rsu/pdb
• Descriptor: DNA polymerase, Template, Primer, ... (4 entities in total)
• Functional Keywords: dna polymerase, transferase, transferase-dna complex, transferase/dna
• Biological source: Thermococcus kodakarensis (Pyrococcus kodakaraensis (strain KOD1)); More
• Total number of polymer chains: 3
• Total formula weight: 99463.53

Authors

Maola, V.,Chaput, J.,Chim, N. (deposition date: 2021-08-11, release date: 2021-10-27, Last modification date: 2023-10-18)

Primary citation

Li, Q.,Maola, V.A.,Chim, N.,Hussain, J.,Lozoya-Colinas, A.,Chaput, J.C.
Synthesis and Polymerase Recognition of Threose Nucleic Acid Triphosphates Equipped with Diverse Chemical Functionalities.
J.Am.Chem.Soc., 143:17761-17768, 2021

PubMed Abstract: Expanding the chemical space of evolvable non-natural genetic polymers (XNAs) to include functional groups that enhance protein target binding affinity offers a promising route to therapeutic aptamers with high biological stability. Here we describe the chemical synthesis and polymerase recognition of 10 chemically diverse functional groups introduced at the C-5 position of α-l-threofuranosyl uridine nucleoside triphosphate (tUTP). We show that the set of tUTP substrates is universally recognized by the laboratory-evolved polymerase Kod-RSGA. Insights into the mechanism of TNA synthesis were obtained from a high-resolution X-ray crystal structure of the postcatalytic complex bound to the primer-template duplex. A structural analysis reveals a large cavity in the enzyme active site that can accommodate the side chain of C-5-modified tUTP substrates. Our findings expand the chemical space of evolvable nucleic acid systems by providing a synthetic route to artificial genetic polymers that are uniformly modified with diversity-enhancing functional groups.

PubMed: 34637287
DOI: 10.1021/jacs.1c08649

Experimental method

X-RAY DIFFRACTION (2.1 Å)