5TT8

Crystal structure of the complex of Helicobacter pylori alpha-carbonic anhydrase with benzolamide

Summary for 5TT8

• Entry DOI: 10.2210/pdb5tt8/pdb
• Related: 5TT3 5TUO 5TV3
• Descriptor: Alpha-carbonic anhydrase, ZINC ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: alpha-carbonic anhydrase, helicobacter pylori, zinc metalloenzyme, lyase
• Biological source: Helicobacter pylori (strain ATCC 700392 / 26695)
• Total number of polymer chains: 8
• Total formula weight: 219012.53

Authors

Modak, J.K.,Roujeinikova, A. (deposition date: 2016-11-02, release date: 2017-09-13, Last modification date: 2024-10-16)

Primary citation

Modak, J.K.,Liu, Y.C.,Supuran, C.T.,Roujeinikova, A.
Structure-Activity Relationship for Sulfonamide Inhibition of Helicobacter pylori alpha-Carbonic Anhydrase.
J. Med. Chem., 59:11098-11109, 2016

PubMed Abstract: α-Carbonic anhydrase of Helicobacter pylori (HpαCA) plays an important role in the acclimation of this oncobacterium to the acidic pH of the stomach. Sulfonamide inhibitors of HpαCA possess anti-H. pylori activity. The crystal structures of complexes of HpαCA 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 HpαCA 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 HpαCA. Thus, our analysis identified major structural features can be exploited in the design of selective and more potent inhibitors of HpαCA that may lead to novel antimicrobials.

PubMed: 28002963
DOI: 10.1021/acs.jmedchem.6b01333

Experimental method

X-RAY DIFFRACTION (2.4 Å)