6WOY

Thermus thermophilus RNA polymerase initially transcribing complex with 3'dCTP

Summary for 6WOY

• Entry DOI: 10.2210/pdb6woy/pdb
• Descriptor: DNA-directed RNA polymerase subunit alpha, ZINC ION, 3'-DEOXY-CYTIDINE-5'-TRIPHOSPHATE, ... (11 entities in total)
• Functional Keywords: initially transcribing complex, transcription, transcription-dna-rna complex, transcription/dna/rna
• Biological source: Thermus thermophilus; More
• Total number of polymer chains: 9
• Total formula weight: 441214.18

Authors

Shin, Y.,Murakami, K.S. (deposition date: 2020-04-26, release date: 2020-06-10, Last modification date: 2023-10-18)

Primary citation

Makinen, J.J.,Shin, Y.,Vieras, E.,Virta, P.,Metsa-Ketela, M.,Murakami, K.S.,Belogurov, G.A.
The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases.
Nat Commun, 12:796-796, 2021

PubMed Abstract: RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2'dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2'OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2'dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here, we show that a conserved Arg residue uses a two-pronged strategy to select against 2'dNTPs in multi-subunit RNAPs. The conserved Arg interacts with the 2'OH group to promote NTP binding, but selectively inhibits incorporation of 2'dNTPs by interacting with their 3'OH group to favor the catalytically-inert 2'-endo conformation of the deoxyribose moiety. This deformative action is an elegant example of an active selection against a substrate that is a substructure of the correct substrate. Our findings provide important insights into the evolutionary origins of biopolymers and the design of selective inhibitors of viral RNAPs.

PubMed: 33542236
DOI: 10.1038/s41467-021-21005-w

Experimental method

X-RAY DIFFRACTION (3 Å)