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

Publisher:
Elsevier
Publication Type:
Journal Article
Citation:
FEBS Letters, 2004, 574 (1), pp. 49 - 54
Issue Date:
2004-01
Full metadata record
Files in This Item:
Filename Description Size
Thumbnail2009004448OK.pdf283.88 kB
Adobe PDF
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 SKADPshikimate complex with an earlier binary SKADP 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.
Please use this identifier to cite or link to this item: