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Carbonic anhydrase II in complex with carboxylic acid-based inhibitors.

ABSTRACT: 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.

SUBMITTER: Lomelino CL

PROVIDER: S-EPMC6404860 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Carbonic anhydrase II in complex with carboxylic acid-based inhibitors.

Lomelino Carrie L CL McKenna Robert R

Acta crystallographica. Section F, Structural biology communications 20190220 Pt 3

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 s ...[more]

PMID: 30839290

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