Structural highlights
Publication Abstract from PubMedalpha-Carbonic anhydrase of Helicobacter pylori (HpalphaCA) plays an important role in the acclimation of this oncobacterium to the acidic pH of the stomach. Sulfonamide inhibitors of HpalphaCA possess anti-H. pylori activity. The crystal structures of complexes of HpalphaCA with a family of acetazolamide-related sulfonamides have been determined. Analysis of the structures revealed that the mode of sulfonamide binding correlates well with their inhibitory activities. In addition, comparisons with the corresponding inhibitor complexes of human carbonic anhydrase II (HCAII) indicated that HpalphaCA possesses an additional, alternative binding site for sulfonamides that is not present in HCAII. Furthermore, the hydrophobic pocket in HCAII that stabilizes the apolar moiety of sulfonamide inhibitors is replaced with a more open, hydrophilic pocket in HpalphaCA. Thus, our analysis identified major structural features can be exploited in the design of selective and more potent inhibitors of HpalphaCA that may lead to novel antimicrobials. Structure-Activity Relationship for Sulfonamide Inhibition of Helicobacter pylori alpha-Carbonic Anhydrase.,Modak JK, Liu YC, Supuran CT, Roujeinikova A J Med Chem. 2016 Dec 22;59(24):11098-11109. doi: 10.1021/acs.jmedchem.6b01333., Epub 2016 Dec 8. PMID:28002963[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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