Structural highlights
Function
AROK_MYCTU Catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid using ATP as a cosubstrate.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase.,Dhaliwal B, Nichols CE, Ren J, Lockyer M, Charles I, Hawkins AR, Stammers DK FEBS Lett. 2004 Sep 10;574(1-3):49-54. PMID:15358538[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Oliveira JS, Pinto CA, Basso LA, Santos DS. Cloning and overexpression in soluble form of functional shikimate kinase and 5-enolpyruvylshikimate 3-phosphate synthase enzymes from Mycobacterium tuberculosis. Protein Expr Purif. 2001 Aug;22(3):430-5. PMID:11483005 doi:10.1006/prep.2001.1457
- ↑ Hartmann MD, Bourenkov GP, Oberschall A, Strizhov N, Bartunik HD. Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis. J Mol Biol. 2006 Dec 1;364(3):411-23. Epub 2006 Sep 5. PMID:17020768 doi:10.1016/j.jmb.2006.09.001
- ↑ Dhaliwal B, Nichols CE, Ren J, Lockyer M, Charles I, Hawkins AR, Stammers DK. Crystallographic studies of shikimate binding and induced conformational changes in Mycobacterium tuberculosis shikimate kinase. FEBS Lett. 2004 Sep 10;574(1-3):49-54. PMID:15358538 doi:10.1016/j.febslet.2004.08.005
