Collagen Hydroxylases and the Protein Disulfide Isomerase Subunit of Prolyl 4-hydroxylases

Adv Enzymol Relat Areas Mol Biol. 1998;72:325-98. doi: 10.1002/9780470123188.ch9.

Abstract

Prolyl 4-hydroxylases catalyze the formation of 4-hydroxyproline in collagens and other proteins with an appropriate collagen-like stretch of amino acid residues. The enzyme requires Fe(II), 2-oxoglutarate, molecular oxygen, and ascorbate. This review concentrates on recent progress toward understanding the detailed mechanism of 4-hydroxylase action, including: (a) occurrence and function of the enzyme in animals; (b) general molecular properties; (c) intracellular sites of hydroxylation; (d) peptide substrates and mechanistic roles of the cosubstrates; (e) insights into the development of antifibrotic drugs; (f) studies of the enzyme's subunits and their catalytic function; and (g) mutations that lead to Ehlers-Danlos Syndrome. An account of the regulation of collagen hydroxylase activities is also provided.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Ehlers-Danlos Syndrome / genetics
  • Humans
  • Molecular Sequence Data
  • Procollagen / metabolism*
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / metabolism*
  • Procollagen-Proline Dioxygenase / genetics
  • Procollagen-Proline Dioxygenase / metabolism*
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism*
  • Protein Processing, Post-Translational
  • Sequence Homology, Amino Acid

Substances

  • Procollagen
  • Procollagen-Proline Dioxygenase
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
  • proline, 2-oxoglutarate 3-dioxygenase
  • Protein Disulfide-Isomerases