REAGENT or RESOURCE	SOURCE	IDENTIFIER
Chemicals, Peptides, and Recombinant Proteins
Taq DNA polymerase	Roche	Cat#11146165001
EarI restriction endonuclease	New England Biolabs	Cat#R0528L
T7 RNA polymerase	This study	Prepared in lab
Inorganic pyrophosphatase	Sigma-Aldrich	Cat#I1643
(+/−)-2-Methyl-2,4-pentanediol	Hampton Research	Cat#HR2-627
Polyethylene glycol 1000 (50% w/v)	Hampton Research	Cat#HR2-523
SuperScript II reverse transcriptase	ThermoFisher Scientific	Cat#18064014
PfuTurbo DNA polymerase	Agilent	Cat#600250
Deposited Data
Crystal structure of the WT P4–P6 domain	Cate et al., 1996	PDB: 1GID
Crystal structure of P4–P6 mutant ΔC209	Juneau et al., 2001	PDB: 1HR2
Crystal structure of P4–P6 mutant U131A (M1) grown under PEG1000 conditions and soaked with isopropanol	This study	PDB: 6BJX
Crystal structure of P4–P6 mutant U131A (M1) grown under MPD conditions and frozen without soaking	This study	PDB: 6D8L
Crystal structure of P4–P6 mutant A125U/G126U (M2)	This study	PDB: 6D8M
Crystal structure of P4–P6 mutant G134A/U185AA (M3)	This study	PDB: 6D8N
Crystal structure of P4–P6 mutant A230U (M4)	This study	PDB: 6D8O
Structure of the S-adenosylmethionine riboswitch	Montange and Batey, 2006	PDB: 2GIS
Structure of the group II intron domains 5 and 6	Zhang and Doudna, 2002	PDB: 1KXK
Experimental Models: Organisms/Strains
E. coli: XL-1 Blue MRF’ electroporation-competent cells: Δ(mcrA)183 Δ(mcrCB-hsdSMR-mrr)173 endA1 supE44 thi-1 recA1 gyrA96 relA1 lac [F’ proAB lacIqZΔM15 Tn10 (Tetr)]	Agilent	Cat#200158
Oligonucleotides
Error-prone PCR forward primer (5′-CAGTGAATTCAATTAATACGACTCACTATAGGAAT-3′)	This study	Synthesized in lab
Error-prone PCR reverse primer (5′-GCAGGTCGACTCTAGACTCTTC-3′)	This study	Synthesized in lab
Reverse transcription primer (5′-TGAACTGCATCCATATCAACAG-3′)	This study	Synthesized in lab
Library amplification forward primer (5′-CAGTGAATTCAATTAATACGACTCACTATAGGAATTGCGGGAAAGGGGTC-3′)	This study	Synthesized in lab
Library amplification reverse primer (5′-CGACTCTAGACTCTTCGTGAACTGCATCCATATCAACAG-3′)	This study	Synthesized in lab
Software and Algorithms
XDS	Kabsch, 2010	http://xds.mpimf-heidelberg.mpg.de/
PHENIX	Adams et al., 2010	https://www.phenix-online.org/
Coot	Emsley et al., 2010	https://www2.mrc-lmb.cam.ac.uk/personal/pemsley/coot/
BUSTER	Smart et al., 2012	https://www.globalphasing.com/buster/
PyMOL	Schrödinger, LLC	https://pymol.org
Prism (version 7)	GraphPad Software	https://www.graphpad.com