Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans

  • Nat Chem Biol. 2012 Dec;8(12):960-962. doi: 10.1038/nchembio.1093.
Wei Ge  #  1 ,  Alexander Wolf  #  1 ,  Tianshu Feng  #  2 ,  Chia-Hua Ho  #  1 ,  Rok Sekirnik  #  1 ,  Adam Zayer  #  2 ,  Nicolas Granatino  1 ,  Matthew E Cockman  2 ,  Christoph Loenarz  1 ,  Nikita D Loik  1 ,  Adam P Hardy  1 ,  Timothy D W Claridge  1 ,  Refaat B Hamed  1 ,  Rasheduzzaman Chowdhury  1 ,  Lingzhi Gong  1 ,  Carol V Robinson  1 ,  David C Trudgian  3 ,  Miao Jiang  1 ,  Mukram M Mackeen  1 ,  James S Mccullagh  1 ,  Yuliya Gordiyenko  1 ,  Armin Thalhammer  1 ,  Atsushi Yamamoto  2 ,  Ming Yang  2 ,  Phebee Liu-Yi  2 ,  Zhihong Zhang  1 ,  Marion Schmidt-Zachmann  4 ,  Benedikt M Kessler  2 ,  Peter J Ratcliffe  #  2 ,  Gail M Preston  #  5 ,  Mathew L Coleman  #  2 ,  Christopher J Schofield  #  1
Affiliations
  • 1. Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
  • 2. Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, OX3 7BN, UK.
  • 3. Biochemistry Dept and Proteomics Core, UT Southwestern Medical Center at Dallas, 6001 Forest Park Rd, Dallas, TX 75390-8816, USA.
  • 4. Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, 69120 Heidelberg, Germany.
  • 5. Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK.
  • # Contributed equally.
PMID: 23103944 DOI: 10.1038/nchembio.1093
Abstract

The finding that oxygenase-catalyzed protein hydroxylation regulates animal transcription raises questions as to whether the translation machinery and prokaryotic proteins are analogously modified. Escherichia coli ycfD is a growth-regulating 2-oxoglutarate oxygenase catalyzing arginyl hydroxylation of the ribosomal protein Rpl16. Human ycfD homologs, Myc-induced nuclear antigen (MINA53) and NO66, are also linked to growth and catalyze histidyl hydroxylation of Rpl27a and Rpl8, respectively. This work reveals new therapeutic possibilities via oxygenase inhibition and by targeting modified over unmodified ribosomes.