The 21st amino acid, selenocysteine (Sec), is synthesized on its dedicated transfer RNA (tRNA). In bacteria, Sec is synthesized from Ser-tRNA by Selenocysteine Synthase (SelA), which is a pivotal enzyme in the biosynthesis of Sec. The structural characterization of bacterial SelA is of paramount importance to decipher its catalytic mechanism and its role in the regulation of the Sec-synthesis pathway. Here, we present a comprehensive single-particle cryo-electron microscopy (SPA cryoEM) structure of the bacterial SelA with an overall resolution of 2.69 Å. Using recombinant SelA, we purified and prepared samples for single-particle cryoEM. The structural insights from SelA, combined with previous and knowledge, underscore the indispensable role of decamerization in SelA's function. Moreover, our structural analysis corroborates previous results that show that SelA adopts a pentamer of dimers configuration, and the active site architecture, substrate binding pocket, and key K295 catalytic residue are identified and described in detail. The differences in protein architecture and substrate coordination between the bacterial enzyme and its counterparts offer compelling structural evidence supporting the independent molecular evolution of the bacterial and archaea/eukarya Ser-Sec biosynthesis present in the natural world.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11047290 | PMC |
| http://dx.doi.org/10.1016/j.crstbi.2024.100143 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Human selenocysteine synthase, SEPSECS, has evolved to optimize binding of a tRNA-based substrate.
Nucleic Acids Res
November 2024
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
Article Synopsis
- The incorporation of selenocysteine (Sec) into the genetic code has led to the creation of a specialized group of proteins, known as the selenoproteome, across all life forms.* -
- In humans, the enzyme O-phosphoseryl-tRNASec selenium transferase (SepSecS) has a unique structure that limits its ability to bind more than two tRNASec molecules, due to a specific acidic α-helical extension.* -
- Research finds that the tRNA-binding mechanisms of SepSecS vary across species, with significant differences between mammals and archaea, indicating that the ability to regulate selenoprotein synthesis has evolved differently in these groups.*
Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).
Biochim Biophys Acta Mol Basis Dis
August 2024
National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India. Electronic address:
Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species.
View Article and Find Full Text PDFBacterial selenocysteine synthase structure revealed by single-particle cryoEM.
Curr Res Struct Biol
April 2024
Physics Institute of Sao Carlos, University of Sao Paulo, Trabalhador Sao Carlense Av., 400, São Carlos, SP, CEP 13566-590, Brazil.
The 21st amino acid, selenocysteine (Sec), is synthesized on its dedicated transfer RNA (tRNA). In bacteria, Sec is synthesized from Ser-tRNA by Selenocysteine Synthase (SelA), which is a pivotal enzyme in the biosynthesis of Sec. The structural characterization of bacterial SelA is of paramount importance to decipher its catalytic mechanism and its role in the regulation of the Sec-synthesis pathway.
View Article and Find Full Text PDFStructure of the Oxygen, Pyridoxal Phosphate-Dependent Capuramycin Biosynthetic Protein Cap15.
Biochemistry
September 2023
Department of Chemistry, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.
Pyridoxal phosphate-dependent enzymes able to use oxygen as a co-substrate have emerged in multiple protein families. Here, we use crystallography to solve the 2.40 Å resolution crystal structure of Cap15, a nucleoside biosynthetic enzyme that catalyzes the oxidative decarboxylation of glycyl uridine.
View Article and Find Full Text PDFRecoding UAG to selenocysteine in .
RNA
September 2023
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511, USA
Unique chemical and physical properties are introduced by inserting selenocysteine (Sec) at specific sites within proteins. Recombinant and facile production of eukaryotic selenoproteins would benefit from a yeast expression system; however, the selenoprotein biosynthetic pathway was lost in the evolution of the kingdom Fungi as it diverged from its eukaryotic relatives. Based on our previous development of efficient selenoprotein production in bacteria, we designed a novel Sec biosynthesis pathway in using translation components.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!