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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 A. 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 degrees. Detailed knowledge of shikimate binding is an important step in the design of inhibitors of SK, which have potential as novel anti-tuberculosis agents.

Original publication

DOI

10.1016/j.febslet.2004.08.005

Type

Journal article

Journal

FEBS Lett

Publication Date

10/09/2004

Volume

574

Pages

49 - 54

Keywords

Cloning, Molecular, Crystallography, X-Ray, Phosphotransferases (Alcohol Group Acceptor), Protein Conformation, Shikimic Acid, Substrate Specificity