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

Lookup NU author(s): Professor Alastair Hawkins

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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.

Publication metadata

Author(s): Dhaliwal B, Nichols CE, Ren J, Lockyer M, Charles I, Hawkins AR, Stammers DK

Publication type: Article

Publication status: Published

Journal: FEBS Letters

Year: 2004

Volume: 574

Issue: 1-3

Pages: 49-54

ISSN (print): 0014-5793

ISSN (electronic): 1873-3468

Publisher: Elsevier BV

URL: http://dx.doi.org/10.1016/j.febslet.2004.08.005

DOI: 10.1016/j.febslet.2004.08.005

PubMed id: 15358538

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