The first activation study of a δ-carbonic anhydrase: TweCAδ from the diatom Thalassiosira weissflogii is effectively activated by amines and amino acids

Andrea Angeli; Fatmah A S Alasmary; Sonia Del Prete; Sameh M Osman; Zeid AlOthman; William A Donald; Clemente Capasso; Claudiu T Supuran

doi:10.1080/14756366.2018.1447570

The first activation study of a δ-carbonic anhydrase: TweCAδ from the diatom Thalassiosira weissflogii is effectively activated by amines and amino acids

J Enzyme Inhib Med Chem. 2018 Dec;33(1):680-685. doi: 10.1080/14756366.2018.1447570.

Authors

Andrea Angeli¹, Fatmah A S Alasmary², Sonia Del Prete^{1

3}, Sameh M Osman², Zeid AlOthman², William A Donald⁴, Clemente Capasso³, Claudiu T Supuran^{1

4}

Affiliations

¹ a Department of Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.
² b Department of Chemistry, College of Science , King Saud University , Riyadh , Saudi Arabia.
³ c Istituto di Bioscienze e Biorisorse , CNR , Napoli , Italy.
⁴ d School of Chemistry , University of New South Wales , Sydney , Australia.

Abstract

The activation of the δ-class carbonic anhydrase (CAs, EC 4.2.1.1) from the diatom Thalassiosira weissflogii (TweCAδ) was investigated using a panel of natural and non-natural amino acids and amines. The most effective activator of TweCAδ was d-Tyr (K_A of 51 nM), whereas several other amino acids and amines, such as L-His, L-Trp, d-Trp, dopamine and serotonin were submicromolar activators (K_As from 0.51 to 0.93 µM). The most ineffective activator of TweCAδ was 4-amino-l-Phe (18.9 µM), whereas d-His, l-/d-Phe, l-/d-DOPA, l-Tyr, histamine, some pyridyl-alkylamines, l-adrenaline and aminoethyl-piperazine/morpholine were moderately potent activators (K_As from 1.34 to 8.16 µM). For any δ-CA, there are no data on the crystal structure, homology modelling and the amino acid residues that are responsible for proton transfer to the active site are currently unknown making it challenging to provide a detailed rational for these findings. However, these data provide further evidence that this class of underexplored CA deserves more attention.

Keywords: Carbonic anhydrase; Thalassiosira weissflogii; activators; diatoms; metalloenzymes.

MeSH terms

Amines / chemistry
Amines / pharmacology*
Amino Acids / chemistry
Amino Acids / pharmacology*
Carbonic Anhydrases / metabolism
Diatoms / enzymology*
Humans
Models, Molecular

Substances

Amines
Amino Acids
Carbonic Anhydrases

Grants and funding

This research was financed in part by a Distinguished Scientist Fellowship Programme (DSFP) of King Saud University, Saudi Arabia to CTS. The Australian Research Council is also acknowledged for support [DP160102681].