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Anion inhibition studies of two new β-carbonic anhydrases from the bacterial pathogen Legionella pneumophila

Research Area: Uncategorized Year: 2014
Type of Publication: Article
Authors:
Journal: Bioorganic and Medicinal Chemistry Letters Volume: 24
Number: 4 Pages: 1127-1132
Note:
cited By (since 1996)0
Abstract:
We investigated the cloning, catalytic activity and anion inhibition of the β-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Legionella pneumophila. Two such enzymes, lpCA1 and lpCA2, were found in the genome of this pathogen. These enzymes were determined to be efficient catalysts for CO2 hydration, with kcat values in the range of (3.4-8.3) × 105 s-1 and kcat/K M values of (4.7-8.5) × 107 M-1 s -1. A set of inorganic anions and small molecules was investigated to identify inhibitors of these enzymes. Perchlorate and tetrafluoroborate were not acting as inhibitors (KI >200 mM), whereas sulfate was a very weak inhibitor for both lpCA1 and lpCA2 (KI values of 77.9-96.5 mM). The most potent lpCA1 inhibitors were cyanide, azide, hydrogen sulfide, diethyldithiocarbamate, sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, with KI values ranging from 6 to 94 μM. The most potent lpCA2 inhibitors were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, with KI values ranging from 2 to 13 μM. As these enzymes seem to be involved in regulation of phagosome pH during Legionella infection, inhibition of these targets may lead to antibacterial agents with a novel mechanism of action. © 2014 Elsevier Ltd. All rights reserved.
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