My NCBISign In

Display Settings:

Format

Send to:

Choose Destination
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13522-6. Epub 2002 Sep 30.

    Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin.

    Jin L, Harrison SC.

    Source

    Department of Molecular and Cellular Biology, and Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.

    Abstract

    Calcineurin (Cn), a Ca(2+)/calmodulin-dependent Ser/Thr protein phosphatase, is an important participant in signaling pathways that activate T cells. It is the target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. These drugs bind proteins known as cyclophilin (Cyp) and FK506-binding protein, respectively, and the drug-protein complexes in turn inhibit Cn. We report the crystal structure of a Cyp/CsA/Cn ternary complex, determined to a resolution of 3.1 A. Residues 3-9 of CsA, particularly N-methyl leucines 4 and 6, and Trp-121 of Cyp form a composite surface for interaction with Cn. The hydrophobic interface buries two hydrogen bonds. The structure accounts clearly for the effects of mutations in Cn on CsA-resistance and for the way modifications of CsA alter immunosuppressive activity.

    PMID:
    12357034
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC129706
    Free PMC Article

    Images from this publication.See all images (3) Free text

    Fig 2.
    Fig 1.
    Fig 3.

    Publication Types, MeSH Terms, Substances, Secondary Source ID

    Publication Types

    MeSH Terms

    Substances

    Secondary Source ID

    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 20 PubMed Central articles

      See all...

      Structures reported by this article

      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.
      • 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.
      • OMIM (calculated)
        Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
      • 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.
      • 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