Structure-based discovery of inhibitors of Helicobacter pylori urease: abridged secondary publication
CL Tam1; MH Yuen1; YS Nim1; YF Xu2; SWN Au1; JCK Ngo1; P Huang2; KB Wong1
1 School of Life Sciences, The Chinese University of Hong Kong
2 College of Chinese Medicine, Guangzhou University of Chinese Medicine
1. Structure-based screening was performed by docking >270 000 ligands to the crystal structures of UreG using the program DOCK.
2. Ranked by the calculated binding energies and a clustering analysis, 73 ligands were selected for in-vitro enzyme assay.
3. The inhibition against UreG was further improved by screening structural analogues of initial hits. The best inhibitors have IC50 values in the range of 20-30 μM.
4. UreG inhibitors identified, like the urease inhibitor acetohydroxamic acid, could suppress the survival of Helicobacter pylori in acid medium, suggesting that inhibiting the urease maturation could be a novel target for inhibiting the growth of H pylori in acid environment.