Angeli Andrea, Alasmary Fatmah A S, Del Prete Sonia, Osman Sameh M, AlOthman Zeid, Donald William A, Capasso Clemente, Supuran Claudiu T
a Department of Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.
b Department of Chemistry, College of Science , King Saud University , Riyadh , Saudi Arabia.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):680-685. doi: 10.1080/14756366.2018.1447570.
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 of 51 nM), whereas several other amino acids and amines, such as L-His, L-Trp, d-Trp, dopamine and serotonin were submicromolar activators (Ks 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 (Ks 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.
利用一组天然和非天然氨基酸及胺类，对来自硅藻威氏海链藻（TweCAδ）的δ类碳酸酐酶（CAs，EC 4.2.1.1）的激活作用进行了研究。TweCAδ最有效的激活剂是d-酪氨酸（K为51 nM），而其他几种氨基酸和胺类，如L-组氨酸、L-色氨酸、d-色氨酸、多巴胺和5-羟色胺是亚微摩尔级激活剂（Ks为0.51至0.93 μM）。TweCAδ最无效的激活剂是4-氨基-L-苯丙氨酸（18.9 μM），而d-组氨酸、L-/d-苯丙氨酸、L-/d-多巴、L-酪氨酸、组胺、一些吡啶基烷基胺、L-肾上腺素和氨乙基哌嗪/吗啉是中等强度的激活剂（Ks为1.34至8.16 μM）。对于任何δ-CA，目前尚无关于晶体结构、同源建模的数据，且负责质子转移至活性位点的氨基酸残基也未知，因此难以对这些发现给出详细的合理解释。然而，这些数据进一步证明，这类未被充分研究的CA值得更多关注。
