• Login
    View Item 
    •   Home
    • UMass Chan Departments, Programs and Centers
    • Biochemistry and Molecular Biotechnology
    • Thompson Lab Publications
    • View Item
    •   Home
    • UMass Chan Departments, Programs and Centers
    • Biochemistry and Molecular Biotechnology
    • Thompson Lab Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsProfilesView

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingUsage StatisticsAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Substrate specificity, processivity, and kinetic mechanism of protein arginine methyltransferase 5.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Wang, Min
    Xu, Rui-Ming
    Thompson, Paul R
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2013-08-13
    Keywords
    Amino Acid Sequence
    Animals
    Arginine
    Caenorhabditis elegans
    Caenorhabditis elegans Proteins
    Catalysis
    Kinetics
    Methylation
    Molecular Sequence Data
    Protein-Arginine N-Methyltransferases
    Substrate Specificity
    Biochemistry
    Enzymes and Coenzymes
    Medicinal-Pharmaceutical Chemistry
    Therapeutics
    Show allShow less
    
    Metadata
    Show full item record
    Link to Full Text
    http://dx.doi.org/10.1021/bi4005123
    Abstract
    Protein arginine methyltransferases (PRMTs) have emerged as attractive therapeutic targets for heart disease and cancers. PRMT5 is a particularly interesting target because it is overexpressed in blood, breast, colon, and stomach cancers and promotes cell survival in the face of DNA damaging agents. As the only known member of the PRMT enzyme family to catalyze the formation of mono- and symmetrically dimethylated arginine residues, PRMT5 is also mechanistically unique. As a part of a program to characterize the mechanisms and regulation of the PRMTs and develop chemical probes targeting these enzymes, we characterized the substrate specificity, processivity, and kinetic mechanism of bacterially expressed Caenorhabditis elegans PRMT5 (cPRMT5). In this report, we demonstrate that distal positively charged residues contribute to substrate binding in a synergistic fashion. Additionally, we show that cPRMT5 catalyzes symmetric dimethylation in a distributive fashion. Finally, the results of initial velocity, product, and dead-end inhibition studies indicate that cPRMT5 uses a rapid equilibrium random mechanism with dead-end EAP and EBQ complexes. In total, these studies will guide PRMT5 inhibitor development and lay the foundation for studying how the activity of this medically relevant enzyme is regulated.
    Source
    Biochemistry. 2013 Aug 13;52(32):5430-40. doi: 10.1021/bi4005123. Epub 2013 Aug 1. Link to article on publisher's site
    DOI
    10.1021/bi4005123
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50013
    Notes

    At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1021/bi4005123
    Scopus Count
    Collections
    Thompson Lab Publications

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Works found in eScholarship@UMassChan are protected by copyright unless otherwise indicated.
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.