Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase

Balvinder Dhaliwal, Charles E. Nichols, Jingshan Ren, Michael Lockyer, Ian Charles, Alastair R. Hawkins, David K. Stammers

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The X-ray crystal structure of Mycobacterium tuberculosis shikimate kinase (SK) with bound shikimate and adenosine diphosphate (ADP) has been determined to a resolution of 2.15 Å. The binding of shikimate in a shikimate kinase crystal structure has not previously been reported. The substrate binds in a pocket lined with hydrophobic residues and interacts with several highly conserved charged residues including Asp34, Arg58, Glu61 and Arg136 which project into the cavity. Comparisons of our ternary SK-ADP-shikimate complex with an earlier binary SK-ADP complex show that conformational changes occur on shikimate binding with the substrate-binding domain rotating by 10°. Detailed knowledge of shikimate binding is an important step in the design of inhibitors of SK, which have potential as novel anti-tuberculosis agents. © 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)49-54
    Number of pages5
    JournalFEBS Letters
    Volume574
    Issue number1-3
    DOIs
    Publication statusPublished - 10 Sept 2004

    Keywords

    • ADP, adenosine diphosphate
    • ATP, adenosine triphosphate
    • Ec, Escherichia coli
    • Erc, Erwinia chrysanthemi
    • Mt, Mycobacterium tuberculosis
    • SD, standard deviation
    • Shikimate kinase
    • Shikimate pathway
    • SK, shikimate kinase
    • TAD, torsion angle difference

    Fingerprint

    Dive into the research topics of 'Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase'. Together they form a unique fingerprint.

    Cite this