8DRB

Crystal structure of Neisseria gonorrhoeae carbonic anhydrase with 3-phenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide

Summary for 8DRB

• Entry DOI: 10.2210/pdb8drb/pdb
• Descriptor: Carbonic anhydrase, 3-phenyl-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)propanamide, ZINC ION, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase, neisseria gonorrhoeae, acetazolamide, lyase
• Biological source: Neisseria gonorrhoeae
• Total number of polymer chains: 4
• Total formula weight: 111926.77

Authors

Marapaka, A.K.,Das, C.,Flaherty, D.P.,Yadav, R. (deposition date: 2022-07-20, release date: 2022-12-14, Last modification date: 2024-11-13)

Primary citation

Marapaka, A.K.,Nocentini, A.,Youse, M.S.,An, W.,Holly, K.J.,Das, C.,Yadav, R.,Seleem, M.N.,Supuran, C.T.,Flaherty, D.P.
Structural Characterization of Thiadiazolesulfonamide Inhibitors Bound to Neisseria gonorrhoeae alpha-Carbonic Anhydrase.
Acs Med.Chem.Lett., 14:103-109, 2023

PubMed Abstract: Drug-resistant is a critical threat to public health, and bacterial carbonic anhydrases expressed by are potential new therapeutic targets to combat this pathogen. To further expand upon our recent reports of bacterial carbonic anhydrase inhibitors for the treatment of , our team has solved ligand-bound crystal structures of the FDA-approved carbonic anhydrase inhibitor acetazolamide, along with three analogs, in complex with the essential α-carbonic anhydrase isoform from . The structural data for the analogs presented bound to α-carbonic anhydrase supports the observed structure-activity relationship for inhibition with this scaffold against the enzyme. Moreover, the ligand-bound structures indicate differences in binding poses compared to those traditionally observed with the close human ortholog carbonic anhydrase II. These results present key differences in inhibitor binding between α-carbonic anhydrase and the human carbonic anhydrase II isoform.

PubMed: 36655133
DOI: 10.1021/acsmedchemlett.2c00471

Experimental method

X-RAY DIFFRACTION (2.59 Å)