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Carbonic anhydrase II in complex with carboxylic acid‐based inhibitors
Author(s) -
Lomelino Carrie L.,
McKenna Robert
Publication year - 2019
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x18018344
Subject(s) - carboxylic acid , carbonic anhydrase , sulfonamide , chemistry , gene isoform , carbonic anhydrase ii , enzyme , biochemistry , stereochemistry , gene
Carbonic anhydrases (CAs) are molecular targets in various diseases. While many sulfonamide‐based drugs are in clinical use, CA inhibitor design is moving towards the incorporation of alternative zinc‐binding groups, such as carboxylic acids, to promote CA isoform‐specific inhibition. Here, X‐ray crystal structures of CA II in complex with nicotinic acid and ferulic acid determined to 1.70 and 1.50 Å resolution, respectively, are reported. Furthermore, the structures of these two compounds are superimposed with previously determined structures to compare the mechanisms of inhibition and the properties of carboxylic acid‐based CA inhibitors. This study examines an important class of alternative, non‐sulfonamide‐based CA inhibitors and provides insight to facilitate the structure‐guided design of CA isoform‐specific inhibitors.