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5-Carboxy-8-hydroxyquinoline is a Broad Spectrum 2-Oxoglutarate Oxygenase Inhibitor which Causes Iron Translocation.
Hopkinson, Richard J; Tumber, Anthony; Yapp, Clarence; Chowdhury, Rasheduzzaman; Aik, WeiShen; Che, Ka Hing; Li, Xuan Shirley; Kristensen, Jan B L; King, Oliver N F; Chan, Mun Chiang; Yeoh, Kar Kheng; Choi, Hwanho; Walport, Louise J; Thinnes, Cyrille C; Bush, Jacob T; Lejeune, Clarisse; Rydzik, Anna M; Rose, Nathan R; Bagg, Eleanor A; McDonough, Michael A; Krojer, Tobias; Yue, Wyatt W; Ng, Stanley S; Olsen, Lars; Brennan, Paul E; Oppermann, Udo; Muller-Knapp, Susanne; Klose, Robert J; Ratcliffe, Peter J; Schofield, Christopher J; Kawamura, Akane.
Afiliação
  • Hopkinson RJ; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Tumber A; Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, U.K.
  • Yapp C; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, OX3 7FZ, UK.
  • Chowdhury R; Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, U.K.
  • Aik W; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Che KH; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Li XS; Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, U.K.
  • Kristensen JBL; Botnar Research Centre, Oxford Biomedical Research Unit, Oxford OX3 7LD, U.K.
  • King ONF; Epigenetic Regulation of Chromatin Function Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, U.K.
  • Chan MC; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Yeoh KK; Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
  • Choi H; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Walport LJ; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Thinnes CC; Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7LD, U.K.
  • Bush JT; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Lejeune C; Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7LD, U.K.
  • Rydzik AM; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Rose NR; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Bagg EA; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • McDonough MA; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Krojer T; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Yue WW; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Ng SS; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Olsen L; Epigenetic Regulation of Chromatin Function Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, U.K.
  • Brennan PE; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Oppermann U; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
  • Muller-Knapp S; Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, U.K.
  • Klose RJ; Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, U.K.
  • Ratcliffe PJ; Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, U.K.
  • Schofield CJ; Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
  • Kawamura A; Structural Genomics Consortium, University of Oxford, Headington, OX3 7DQ, U.K.
Chem Sci ; 4(8): 3110-3117, 2013 Aug 01.
Article em En | MEDLINE | ID: mdl-26682036
ABSTRACT
2-Oxoglutarate and iron dependent oxygenases are therapeutic targets for human diseases. Using a representative 2OG oxygenase panel, we compare the inhibitory activities of 5-carboxy-8-hydroxyquinoline (IOX1) and 4-carboxy-8-hydroxyquinoline (4C8HQ) with that of two other commonly used 2OG oxygenase inhibitors, N-oxalylglycine (NOG) and 2,4-pyridinedicarboxylic acid (2,4-PDCA). The results reveal that IOX1 has a broad spectrum of activity, as demonstrated by the inhibition of transcription factor hydroxylases, representatives of all 2OG dependent histone demethylase subfamilies, nucleic acid demethylases and γ-butyrobetaine hydroxylase. Cellular assays show that, unlike NOG and 2,4-PDCA, IOX1 is active against both cytosolic and nuclear 2OG oxygenases without ester derivatisation. Unexpectedly, crystallographic studies on these oxygenases demonstrate that IOX1, but not 4C8HQ, can cause translocation of the active site metal, revealing a rare example of protein ligand-induced metal movement.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies Idioma: En Revista: Chem Sci Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies Idioma: En Revista: Chem Sci Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Reino Unido