ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-07-31
    Description: The jumonji (JMJ) family of histone demethylases are Fe2+- and alpha-ketoglutarate-dependent oxygenases that are essential components of regulatory transcriptional chromatin complexes. These enzymes demethylate lysine residues in histones in a methylation-state and sequence-specific context. Considerable effort has been devoted to gaining a mechanistic understanding of the roles of histone lysine demethylases in eukaryotic transcription, genome integrity and epigenetic inheritance, as well as in development, physiology and disease. However, because of the absence of any selective inhibitors, the relevance of the demethylase activity of JMJ enzymes in regulating cellular responses remains poorly understood. Here we present a structure-guided small-molecule and chemoproteomics approach to elucidating the functional role of the H3K27me3-specific demethylase subfamily (KDM6 subfamily members JMJD3 and UTX). The liganded structures of human and mouse JMJD3 provide novel insight into the specificity determinants for cofactor, substrate and inhibitor recognition by the KDM6 subfamily of demethylases. We exploited these structural features to generate the first small-molecule catalytic site inhibitor that is selective for the H3K27me3-specific JMJ subfamily. We demonstrate that this inhibitor binds in a novel manner and reduces lipopolysaccharide-induced proinflammatory cytokine production by human primary macrophages, a process that depends on both JMJD3 and UTX. Our results resolve the ambiguity associated with the catalytic function of H3K27-specific JMJs in regulating disease-relevant inflammatory responses and provide encouragement for designing small-molecule inhibitors to allow selective pharmacological intervention across the JMJ family.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691848/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691848/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruidenier, Laurens -- Chung, Chun-wa -- Cheng, Zhongjun -- Liddle, John -- Che, KaHing -- Joberty, Gerard -- Bantscheff, Marcus -- Bountra, Chas -- Bridges, Angela -- Diallo, Hawa -- Eberhard, Dirk -- Hutchinson, Sue -- Jones, Emma -- Katso, Roy -- Leveridge, Melanie -- Mander, Palwinder K -- Mosley, Julie -- Ramirez-Molina, Cesar -- Rowland, Paul -- Schofield, Christopher J -- Sheppard, Robert J -- Smith, Julia E -- Swales, Catherine -- Tanner, Robert -- Thomas, Pamela -- Tumber, Anthony -- Drewes, Gerard -- Oppermann, Udo -- Patel, Dinshaw J -- Lee, Kevin -- Wilson, David M -- 092809/Wellcome Trust/United Kingdom -- 18358/Arthritis Research UK/United Kingdom -- P30 CA008748/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Aug 16;488(7411):404-8. doi: 10.1038/nature11262.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Medicines Research Centre, Stevenage SG1 2NY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22842901" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Biocatalysis/drug effects ; Catalytic Domain ; Cells, Cultured ; Enzyme Inhibitors/metabolism/*pharmacology ; Evolution, Molecular ; Histones/chemistry/metabolism ; Humans ; Inhibitory Concentration 50 ; Jumonji Domain-Containing Histone Demethylases/*antagonists & ; inhibitors/chemistry/classification/metabolism ; Lysine/metabolism ; Macrophages/*drug effects/enzymology/*immunology/metabolism ; Methylation/drug effects ; Mice ; Models, Molecular ; Substrate Specificity ; Tumor Necrosis Factor-alpha/biosynthesis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Kruidenier et al. reply (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruidenier, Laurens -- Chung, Chun-wa -- Cheng, Zhongjun -- Liddle, John -- Che, KaHing -- Joberty, Gerard -- Bantscheff, Marcus -- Bountra, Chas -- Bridges, Angela -- Diallo, Hawa -- Eberhard, Dirk -- Hutchinson, Sue -- Jones, Emma -- Katso, Roy -- Leveridge, Melanie -- Mander, Palwinder K -- Mosley, Julie -- Ramirez-Molina, Cesar -- Rowland, Paul -- Schofield, Christopher J -- Sheppard, Robert J -- Smith, Julia E -- Swales, Catherine -- Tanner, Robert -- Thomas, Pamela -- Tumber, Anthony -- Drewes, Gerard -- Oppermann, Udo -- Patel, Dinshaw J -- Lee, Kevin -- Wilson, David M -- 092809/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Oct 2;514(7520):E2. doi: 10.1038/nature13689.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK. ; Platform Technology and Science, GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK. ; Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA. ; 1] Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Headington OX3 7DQ, UK [2] Botnar Research Centre, NIHR Biomedical Research Unit, University of Oxford OX3 7LD, UK. ; Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Headington OX3 7DQ, UK. ; Botnar Research Centre, NIHR Biomedical Research Unit, University of Oxford OX3 7LD, UK. ; 1] Epinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK [2] Pfizer, Biotherapeutics R&D, 200 Cambridgepark Drive, Cambridge, Massachusetts 02140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279927" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Inhibitors/*pharmacology ; Humans ; Jumonji Domain-Containing Histone Demethylases/*antagonists & inhibitors ; Macrophages/*drug effects/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    Phagocytosis executes delayed neuronal death after focal brain ischemia (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-10-07
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Phagocytic neuronal death in brain ischemia [Neuroscience] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-10-23
    Description: Delayed neuronal loss and brain atrophy after cerebral ischemia contribute to stroke and dementia pathology, but the mechanisms are poorly understood. Phagocytic removal of neurons is generally assumed to be beneficial and to occur only after neuronal death. However, we report herein that inhibition of phagocytosis can prevent delayed loss...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...