Regulation of the Stoichiometry of the Human Selenocysteine Synthase (SepSecS) Catalytic Complex

• DOI: 10.1096/fasebj.31.1_supplement.802.18
• Publication Date: 2023-11-26T17:55:47Z
• Authors: Anupama K. Puppala; Miljan Simonovic
• Keywords: Selenocysteine

Selenium is an essential micronutrient for human health. The biologically active form of selenium in all domains life the 21 st amino acid, selenocysteine (Sec). incorporation Sec into proteins unique compared to standard acids as encoded by a UGA stop codon and directly synthesized from serine precursor on its cognate tRNA, tRNA . Although not well understood, biosynthesis requires three enzymes archaea eukaryotes. enzyme synthase (SepSecS) tetrameric that catalyzes terminal reaction synthesis which phosphoseryl intermediate converted selenocysteinyl moiety while attached Our previous studies have demonstrated SepSecS, despite containing four equivalent tRNA‐binding sites active‐site grooves, only binds one or two substrate molecules at given time. Recent structural data provided potential explanation this restriction stoichiometry SepSecS catalytic complex. High‐resolution electron density maps SepSecS‐tRNA complex revealed previously unobserved α‐helix positioned binding site noncatalytic subunits tetramer. This helix interacts with residues are critical recognition binding. Thus, presence precludes additional molecule. disordered structure holoenzyme, suggesting ‐free state equally available suggest model allosteric regulation single molecule leads conformational change prevents sites. Support Funding Information work was supported grant National Institute General Medical Sciences Institutes Health R01 GM097042.