• Login
    View Item 
    •   Home
    • Research
    • Articles
    • View Item
    •   Home
    • Research
    • Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of KAUSTCommunitiesIssue DateSubmit DateThis CollectionIssue DateSubmit Date

    My Account

    Login

    Quick Links

    Open Access PolicyORCID LibguideTheses and Dissertations LibguideSubmit an Item

    Statistics

    Display statistics

    Probing the reaction mechanism of IspH protein by x-ray structure analysis

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Type
    Article
    Authors
    Gräwert, Tobias
    Span, Ingrid
    Eisenreich, Wolfgang
    Rohdich, Felix
    Eppinger, Jörg cc
    Bacher, Adelbert
    Groll, Michael
    KAUST Department
    Biological & Organometallic Catalysis Laboratories
    Biological and Environmental Sciences and Engineering (BESE) Division
    Chemical Science Program
    KAUST Catalysis Center (KCC)
    Physical Science and Engineering (PSE) Division
    Date
    2009-12-28
    Online Publication Date
    2009-12-28
    Print Publication Date
    2010-01-19
    Permanent link to this record
    http://hdl.handle.net/10754/561445
    
    Metadata
    Show full item record
    Abstract
    Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) represent the two central intermediates in the biosynthesis of isoprenoids. The recently discovereddeoxyxylulose 5-phosphate pathway generates a mixture of IPP and DMAPP in its final step by reductive dehydroxylation of 1-hydroxy-2-methyl- 2-butenyl 4-diphosphate. This conversion is catalyzed by IspH protein comprising a central iron-sulfur cluster as electron transfer cofactor in the active site. The five crystal structures of IspH in complex with substrate, converted substrate, products and PPi reported in this article provide unique insights into the mechanism of this enzyme. While IspH protein crystallizes with substrate bound to a [4Fe-4S] cluster, crystals of IspH in complex with IPP, DMAPP or inorganic pyrophosphate feature [3Fe-4S] clusters. The IspH:substrate complex reveals a hairpin conformation of the ligand with the C(1) hydroxyl group coordinated to the unique site in a [4Fe-4S] cluster of aconitase type. The resulting alkoxide complex is coupled to a hydrogen-bonding network, which serves as proton reservoir via a Thr167 proton relay. Prolonged x-ray irradiation leads to cleavage of the C(1)-O bond (initiated by reducing photo electrons). The data suggest a reaction mechanism involving a combination of Lewis-acid activation and proton coupled electron transfer. The resulting allyl radical intermediate can acquire a second electron via the iron-sulfur cluster. The reaction may be terminated by the transfer of a proton from the β-phosphate of the substrate to C(1) (affording DMAPP) or C(3) (affording IPP).
    Citation
    Grawert, T., Span, I., Eisenreich, W., Rohdich, F., Eppinger, J., Bacher, A., & Groll, M. (2009). Probing the reaction mechanism of IspH protein by x-ray structure analysis. Proceedings of the National Academy of Sciences, 107(3), 1077–1081. doi:10.1073/pnas.0913045107
    Publisher
    Proceedings of the National Academy of Sciences
    Journal
    Proceedings of the National Academy of Sciences
    DOI
    10.1073/pnas.0913045107
    PubMed ID
    20080550
    PubMed Central ID
    PMC2824267
    Additional Links
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824267
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.0913045107
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Physical Science and Engineering (PSE) Division; Chemical Science Program; KAUST Catalysis Center (KCC)

    entitlement

    Related articles

    • Broken-Symmetry DFT Computations for the Reaction Pathway of IspH, an Iron-Sulfur Enzyme in Pathogenic Bacteria.
    • Authors: Blachly PG, Sandala GM, Giammona DA, Bashford D, McCammon JA, Noodleman L
    • Issue date: 2015 Jul 6
    • A closer look at the spectroscopic properties of possible reaction intermediates in wild-type and mutant (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase.
    • Authors: Xu W, Lees NS, Hall D, Welideniya D, Hoffman BM, Duin EC
    • Issue date: 2012 Jun 19
    • Exceptionally high percentage of IPP synthesis by Ginkgo biloba IspH is mainly due to Phe residue in the active site.
    • Authors: Shin BK, Kim M, Han J
    • Issue date: 2017 Apr
    • Crystal structures of mutant IspH proteins reveal a rotation of the substrate's hydroxymethyl group during catalysis.
    • Authors: Span I, Gräwert T, Bacher A, Eisenreich W, Groll M
    • Issue date: 2012 Feb 10
    • IspH protein of Escherichia coli: studies on iron-sulfur cluster implementation and catalysis.
    • Authors: Gräwert T, Kaiser J, Zepeck F, Laupitz R, Hecht S, Amslinger S, Schramek N, Schleicher E, Weber S, Haslbeck M, Buchner J, Rieder C, Arigoni D, Bacher A, Eisenreich W, Rohdich F
    • Issue date: 2004 Oct 13
    DSpace software copyright © 2002-2023  DuraSpace
    Quick Guide | Contact Us | KAUST University Library
    Open Repository is a service hosted 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. For anonymous users the allowed maximum amount is 50 search results.

    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.