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

Journal article

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.

Authors: Dhaliwal, B; Nichols, C; Ren, J; Lockyer, M; Charles, I

• Publication status: Published
• Journal: FEBS letters
• Volume: 574
• Issue: 1-3
• Pages: 49-54
• Publication date: 2004-09-01
• DOI: 10.1016/j.febslet.2004.08.005
• EISSN: 1873-3468
• ISSN: 0014-5793
• Language: English
• Keywords: Shikimic Acid; Crystallography, X-Ray; Cloning, Molecular; Substrate Specificity; Protein Conformation; Phosphotransferases (Alcohol Group Acceptor)