3HR7

Crystal structure of the shikimate kinase-sulfate complex from Helicobacter pylori

Summary for 3HR7

• Entry DOI: 10.2210/pdb3hr7/pdb
• Related: 1ZUH 1ZUI
• Descriptor: Shikimate kinase, SULFATE ION (3 entities in total)
• Functional Keywords: three-layer alpha/beta fold, nucleoside monophosphate (nmp) kinase family, amino-acid biosynthesis, aromatic amino acid biosynthesis, atp-binding, kinase, magnesium, metal-binding, nucleotide-binding, transferase
• Biological source: Helicobacter pylori
• Cellular location: Cytoplasm (Probable): P56073
• Total number of polymer chains: 2
• Total formula weight: 38722.80

Authors

Cheng, W.C.,Wang, W.C. (deposition date: 2009-06-09, release date: 2010-06-16, Last modification date: 2023-11-01)

Primary citation

Cheng, W.C.,Chen, Y.F.,Wang, H.J.,Hsu, K.C.,Lin, S.C.,Chen, T.J.,Yang, J.M.,Wang, W.C.
Structures of Helicobacter pylori shikimate kinase reveal a selective inhibitor-induced-fit mechanism
Plos One, 7:e33481-e33481, 2012

PubMed Abstract: Shikimate kinase (SK), which catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP, is the enzyme in the fifth step of the shikimate pathway for biosynthesis of aromatic amino acids. This pathway is present in bacteria, fungi, and plants but absent in mammals and therefore represents an attractive target pathway for the development of new antimicrobial agents, herbicides, and antiparasitic agents. Here we investigated the detailed structure-activity relationship of SK from Helicobacter pylori (HpSK). Site-directed mutagenesis and isothermal titration calorimetry studies revealed critical conserved residues (D33, F48, R57, R116, and R132) that interact with shikimate and are therefore involved in catalysis. Crystal structures of HpSK·SO(4), R57A, and HpSK•shikimate-3-phosphate • ADP show a characteristic three-layer architecture and a conformationally elastic region consisting of F48, R57, R116, and R132, occupied by shikimate. The structure of the inhibitor complex, E114A • 162535, was also determined, which revealed a dramatic shift in the elastic LID region and resulted in conformational locking into a distinctive form. These results reveal considerable insight into the active-site chemistry of SKs and a selective inhibitor-induced-fit mechanism.

PubMed: 22438938
DOI: 10.1371/journal.pone.0033481

Experimental method

X-RAY DIFFRACTION (1.8 Å)