Del Prete Sonia, Vullo Daniela, Scozzafava Andrea, Capasso Clemente, Supuran Claudiu T
Istituto di Biochimica delle Proteine and Institute of Bioscience and Bioresources (IBBR)-CNR, Via P. Castellino 111, 80131 Napoli, Italy.
Università degli Studi di Firenze, Dipartmento di Chimica Ugo Schiff, Via della Lastruccia 3, Rm. 188, 50019 Sesto Fiorentino (Florence), Italy.
Bioorg Med Chem. 2014 Jan 1;22(1):531-7. doi: 10.1016/j.bmc.2013.10.045. Epub 2013 Nov 7.
We investigated the catalytic activity and inhibition of the δ-class carbonic anhydrase (CA, EC 4.2.1.1) from the marine diatom Thalassiosira weissflogii, TweCA. The enzyme, obtained by cloning the synthetic gene, was an efficient catalyst for the CO₂ hydration, its physiological reaction, with a kcat of 1.3 × 10(5)s(-1) and a k(cat)/K(M) of 3.3 × 10(7)M(-1)s(-1). A range of inorganic anions and small molecules were investigated as inhibitors of TweCA. Chloride and sulfate did not inhibit the enzyme (KIs >200 mM) whereas other halides and pseudohalides were submillimolar-millimolar inhibitors (K(I)s in the range of 0.93-8.3 mM). The best TweCA inhibitors were hydrogen sulfide, sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, with K(I)s in the range of 9-90 μM, whereas acetazolamide inhibited the enzyme with a K(I) of 83 nM. This is the first kinetic and inhibition study of a δ-class CA. However, these enzymes are widespread in the marine phytoplankton, being present in haptophytes, dinoflagellates, diatoms, and chlorophytic prasinophytes, contributing to the CO₂ fixation by sea organisms. A phylogenetic analysis with all five genetic families of CAs showed that α- and δ-CAs are evolutionarily more related to each other with respect to the γ-CAs, although these three families clustered all together. On the contrary, the β- and ζ-CAs are also related to each other but phylogenetically much more distant from the α-, γ and δ-CA cluster. Thus, the study of δ-CAs is essential for better understanding this superfamily of metalloenzymes and their potential biotechnological applications in biomimetic CO₂ capture processes, as these enzymes are part of the carbon concentrating mechanism used by many photosynthetic organisms.
我们研究了海洋硅藻威氏海链藻(Thalassiosira weissflogii)的δ-类碳酸酐酶(CA,EC 4.2.1.1,简称TweCA)的催化活性及抑制作用。通过克隆合成基因获得的该酶,是二氧化碳水合反应(其生理反应)的高效催化剂,催化常数(kcat)为1.3×10⁵ s⁻¹,催化效率(kcat/KM)为3.3×10⁷ M⁻¹ s⁻¹。我们研究了一系列无机阴离子和小分子作为TweCA抑制剂的情况。氯离子和硫酸根离子不抑制该酶(抑制常数KIs>200 mM),而其他卤化物和拟卤化物是亚毫摩尔至毫摩尔级别的抑制剂(抑制常数KIs在0.93 - 8.3 mM范围内)。TweCA的最佳抑制剂是硫化氢、氨基磺酸、磺胺、苯硼酸和苯胂酸,抑制常数KIs在9 - 90 μM范围内,而乙酰唑胺抑制该酶的抑制常数KIs为83 nM。这是首次对δ-类CA进行的动力学和抑制研究。然而,这些酶在海洋浮游植物中广泛存在,存在于定鞭藻、甲藻、硅藻和绿藻门的原绿藻中,有助于海洋生物固定二氧化碳。对所有五个CA基因家族进行的系统发育分析表明,尽管这三个家族聚集在一起,但α-和δ-CAs在进化上彼此之间的关系比与γ-CAs的关系更密切。相反,β-和ζ-CAs彼此之间也有关系,但在系统发育上与α-、γ-和δ-CA簇的距离要远得多。因此,研究δ-CAs对于更好地理解这个金属酶超家族及其在仿生二氧化碳捕获过程中的潜在生物技术应用至关重要,因为这些酶是许多光合生物所使用的碳浓缩机制的一部分。