The selenophosphate synthetase family: A review

Free Radic Biol Med. 2022 Nov 1:192:63-76. doi: 10.1016/j.freeradbiomed.2022.09.007. Epub 2022 Sep 16.

Abstract

Selenophosphate synthetases use selenium and ATP to synthesize selenophosphate. This is required for biological utilization of selenium, most notably for the synthesis of the non-canonical amino acid selenocysteine (Sec). Therefore, selenophosphate synthetases underlie all functions of selenoproteins, which include redox homeostasis, protein quality control, hormone regulation, metabolism, and many others. This protein family comprises two groups, SelD/SPS2 and SPS1. The SelD/SPS2 group represent true selenophosphate synthetases, enzymes central to selenium metabolism which are present in all Sec-utilizing organisms across the tree of life. Notably, many SelD/SPS2 proteins contain Sec as catalytic residue in their N-terminal flexible selenium-binding loop, while others replace it with cysteine (Cys). The SPS1 group comprises proteins originated through gene duplications of SelD/SPS2 in metazoa in which the Sec/Cys-dependent catalysis was disrupted. SPS1 proteins do not synthesize selenophosphate and are not required for Sec synthesis. They have essential regulatory functions related to redox homeostasis and pyridoxal phosphate, which affect signaling pathways for growth and differentiation. In this review, we summarize the knowledge about the selenophosphate synthetase family acquired through decades of research, encompassing their structure, mechanism, function, and evolution.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cysteine
  • Hormones
  • Ligases
  • Phosphates
  • Phosphotransferases / genetics
  • Pyridoxal Phosphate
  • Selenium Compounds
  • Selenium* / metabolism
  • Selenocysteine* / metabolism
  • Selenoproteins / metabolism

Substances

  • Hormones
  • Phosphates
  • Selenium Compounds
  • Selenoproteins
  • Selenocysteine
  • selenophosphate
  • Pyridoxal Phosphate
  • Adenosine Triphosphate
  • Phosphotransferases
  • selenophosphate synthetase
  • Ligases
  • Selenium
  • Cysteine