Crystal structures of Helicobacter pylori type II dehydroquinase inhibitor complexes: new directions for inhibitor design.
Basic Information
ID: ALA1149420
Journal: J Med Chem
Title: Crystal structures of Helicobacter pylori type II dehydroquinase inhibitor complexes: new directions for inhibitor design.
Authors: Robinson DA, Stewart KA, Price NC, Chalk PA, Coggins JR, Lapthorn AJ.
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.
CiteXplore: 16480265
DOI: 10.1021/jm0505361
Patent ID: ┄