Crystal structures of Helicobacter pylori type II dehydroquinase inhibitor complexes: new directions for inhibitor design.
Article Details
- CitationCopy to clipboard
Robinson DA, Stewart KA, Price NC, Chalk PA, Coggins JR, Lapthorn AJ
Crystal structures of Helicobacter pylori type II dehydroquinase inhibitor complexes: new directions for inhibitor design.
J Med Chem. 2006 Feb 23;49(4):1282-90.
- PubMed ID
- 16480265 [ View in PubMed]
- Abstract
The crystal structures of the type II dehydroquinase (DHQase) from Helicobacter pylori in complex with three competitive inhibitors have been determined. The inhibitors are the substrate analogue 2,3-anhydroquinate (FA1), citrate, and an oxoxanthene sulfonamide derivative (AH9095). Despite the very different chemical nature of the inhibitors, in each case the primary point of interaction with the enzyme is via the residues that bind the C1 functionalities of the substrate, 3-dehydroquinate, i.e., N76, H102, I103, and H104. The DHQase/AH9095 complex crystal structure shows that sulfonamides can form a scaffold for nonsubstrate-like inhibitors and identifies a large conserved hydrophobic patch at the entrance to the active site as a locus that can be exploited in the development of new ligands.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID 3-dehydroquinate dehydratase Q48255 Details - Binding Properties
Drug Target Property Measurement pH Temperature (°C) 2,3-Anhydro-quinic acid 3-dehydroquinate dehydratase Kd (nM) 200000 N/A N/A Details