title: Structure, mechanism, and evolution of Ero1 family enzymes.
abstract: CONCLUSIONS
  Disulfide bond formation is an essential reaction involved in the folding and maturation of many secreted and membrane proteins. Both prokaryotic and eukaryotic cells utilize various disulfide oxidoreductases and redox-active cofactors to accelerate this oxidative reaction, and higher eukaryotes have diversified and refined these disulfide-introducing cascades over the course of evolution.
  
  
  BACKGROUND
  In the past decade, atomic resolution structures have been solved for an increasing number of disulfide oxidoreductases, thereby revealing the structural and mechanistic basis of cellular disulfide bond formation systems.
  
  
  RESULTS
  In this review, we focus on the evolution, structure, and regulatory mechanisms of endoplasmic reticulum oxidoreductin 1 (Ero1) family enzymes, the primary disulfide bond-generating catalysts in the endoplasmic reticulum (ER). Detailed comparison of Ero1 with other oxidoreductases, such as Prx4, QSOX, Erv1/2, and disulfide bond protein B (DsbB), provides important insight into how this ER-resident flavoenzyme acts in a regulated and specific manner to maintain redox and protein homeostasis in eukaryotic cells.
  
  
  CONCLUSIONS
  Currently, it is presumed that multiple pathways in addition to that mediated by Ero1 cooperate to achieve oxidative folding of many secretory and membrane proteins in mammalian cells. The important open question is how each oxidative pathway works distinctly or redundantly in response to various cellular conditions.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Kyoto Sangyo University, Kyoto, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Araki
authors.forename: Kenji
authors.initials: K
authors.lastname: Inaba
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D019143:Evolution, Molecular; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational
chemical_list: D004220:Disulfides; D008562:Membrane Glycoproteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C485767:ERO1B protein, human; D019704:Protein Disulfide-Isomerases