Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic bacterium Pseudoalteromonas haloplanktis

被引：25

作者：

Vullo, Daniela ^{[1
]}

De Luca, Viviana ^{[2
]}

Del Prete, Sonia ^{[2
,3
]}

Carginale, Vincenzo ^{[2
]}

Scozzafava, Andrea ^{[1
]}

Capasso, Clemente ^{[2
]}

Supuran, Claudiu T. ^{[1
,3
]}

机构：

[1] Univ Florence, Dipartimento Chim, Lab Chim Bioinorgan, Polo Sci, I-50019 Florence, Italy

[2] CNR, Ist Biosci & Biorisorse, I-80125 Naples, Italy

[3] Univ Florence, Dipartimento Neurofarba, Sez Sci Farmaceut, Polo Sci, I-50019 Florence, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 17期

关键词：

Carbonic anhydrase; Metalloenzymes; Inhibitors; Sulfonamide; Psychrophiles; Hydratase activity; Antarctic carbonic anhydrase; Cold adaptation; Cold enzymes; SULFURIHYDROGENIBIUM-YELLOWSTONENSE YO3AOP1; PATHOGEN PORPHYROMONAS-GINGIVALIS; DIATOM THALASSIOSIRA-WEISSFLOGII; FISH NOTOTHENIA-CORIICEPS; ANION INHIBITION; BIOCHEMICAL-CHARACTERIZATION; CHIONODRACO-HAMATUS; MESSENGER-RNA; METALLOTHIONEIN ISOFORMS; LEGIONELLA-PNEUMOPHILA;

D O I：

10.1016/j.bmcl.2015.06.079

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The Antarctic bacterium Pseudoalteromonas haloplanktis encodes for a gamma-class carbonic anhydrase (CA, EC 4.2.1.1), which was cloned, purified and characterized. The enzyme (PhaCA gamma) has a good catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a k(cat) of 1.4 x 10(5) s(-1) and a k(cat)/K-m of 1.9 x 10(6) M-1 x s(-1). A series of sulfonamides and a sulfamate were investigated as inhibitors of the new enzyme. Methazolamide and indisulam showed the best inhibitory properties (K(I)s of 86.7-94.7 nM). This contribution shed new light on gamma-CAs inhibition profiles with a relevant class of pharmacologic agents. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：3550 / 3555

页数：6

共 62 条

[1] Comparative sequence and structure analysis reveal features of cold adaptation of an enzyme in the thermolysin family [J].