Table 1.

Protein structure prediction results for the two GSTCD isoforms using three models I-TASSER, SWISS- MODEL and Phyre2. Methyltransferase (MTF) enzymes are frequently found in the top 3 structural templates listed for each server and the top 50 template results in SWISS-MODEL were entirely methyltransferase proteins, with specific focus on rRNA methyltransferase function. Alternatively, I-TASSER identified homology in this region with transport receptors, specifically importin β subunit 1, involved in transporting proteins into the nucleus [25]. Other top hits included: exodeoxyribonuclease (catalyses degradation of double stranded DNA), Ras guanyl-releasing protein 1 (nucleotide exchange factor specifically activating Ras, activates the extracellular signal-regulated kinases/mitogen-activated protein kinase (ERK/MAPK) cascade) and nicotinamide adenine dinucleotide binding (NADB)-Rossmann fold superfamily protein (structural motif found in proteins that bind nucleotides)

Protein Structure Results	I-TASSER		SWISS-MODEL		Phyre2
	Variant 1	Variant 2	Variant 1	Variant 2	Variant 1	Variant 2
Predicted Secondary Structure	Primarily α-helices with intermittent coil structures. β-strands only present at termini.		N/A		Primarily intermittent α-helices (45%). β-strands only present at termini (12%). Two predicted transmembrane regions (30-40aa and 281-299aa).	Primarily intermittent α-helices (55%). β-strands only present at termini (10%). Two predicted transmembrane regions (29-38aa and 194-212aa).
Regions of Primary Sequence Homology	Primarily across the MTF domain to C-terminus. Partial matches across whole protein.		Only across the MTF domain to C-terminus		Only across the MTF domain
Intrinsic disorder	N/A		Low disorder across C-terminus	High disorder across C-terminus	Two theoretical central regions of disorder (27%):• 204-270aa• 325-386aa	Two theoretical central regions of disorder (26%):• 118-184aa• 257-299aa
Top 3 Structural Templates	Putative MTF Importin β subunit Exodeoxyribonuclease	Ras guanyl-releasing protein 1 MTF	Protein RdmB MTF Protein RdmB MTF Protein RdmB MTF	Putative rRNA methylase Putative rRNA methylase rRNA small subunit MTF	rRNA small subunit MTF Transferase S-adenosyl-L-methionine-dependent MTF	Transferase NADB-Rossmann fold superfamily protein S-adenosyl-L-methionine-dependent MTF