My NCBISign In

Display Settings:

Format

Send to:

Choose Destination
    J Biol Chem. 2008 Apr 25;283(17):11355-63. Epub 2008 Feb 19.

    Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.

    Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH.

    Source

    Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L5, Canada.

    Abstract

    Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

    PMID:
    18285338
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2431080
    Free PMC Article

    Images from this publication.See all images (4) Free text

    FIGURE 1.
    FIGURE 3.
    FIGURE 2.
    FIGURE 4.

    Publication Types, MeSH Terms, Substances, Secondary Source ID, Grant Support

    Publication Types

    MeSH Terms

    Substances

    Secondary Source ID

    Grant Support

    LinkOut - more resources

    Full Text Sources

    Molecular Biology Databases

      Supplemental Content

      Icon for HighWire Press Icon for PubMed Central

      Save items

      loading

      Related citations in PubMed

      See reviews... See all...

      Cited by 28 PubMed Central articles

      See all...

      Structures reported by this article

      See all 3 structures...

      Related information

      • Related Citations
        Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
      • Compound (MeSH Keyword)
        PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • Gene
        Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
      • Gene (GeneRIF)
        Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
      • HomoloGene
        HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
      • Nucleotide (RefSeq)
        NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Nucleotide (Weighted)
        Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
      • Protein (RefSeq)
        NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
      • Protein (Weighted)
        Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
      • References for this PMC Article
        Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.
      • Substance (MeSH Keyword)
        PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • Taxonomy via GenBank
        Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
      • UniGene
        UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
      • Domains
        Conserved Domain Database (CDD) records that cite the current articles. Citations are from the CDD source database records (PFAM, SMART).
      • Protein
        Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
      • Structure
        Three-dimensional structure records in the NCBI Structure database for data reported in the current articles.
      • GEO Profiles
        Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
      • Free in PMC
        Free full text articles in PMC
      • Cited in PMC
        Full-text articles in the PubMed Central Database that cite the current articles.

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...
      You are here: NCBI > Literature > PubMed
      Write to the Help Desk