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比较基因组学编码的α-碳酸酐酶同工型(SpiCA1、SpiCA2 和 SpiCA3)的磺胺抑制谱。

Comparison of the Sulfonamide Inhibition Profiles of the α-Carbonic Anhydrase Isoforms (SpiCA1, SpiCA2 and SpiCA3) Encoded by the Genome of the Scleractinian Coral .

机构信息

Istituto di Bioscienze e Biorisorse, National Research Council (CNR), Via Pietro Castellino 111, 80131 Napoli, Italy.

Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.

出版信息

Mar Drugs. 2019 Mar 1;17(3):146. doi: 10.3390/md17030146.

DOI:10.3390/md17030146
PMID:30832211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6471618/
Abstract

The ubiquitous metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) are responsible for the reversible hydration of CO₂ to bicarbonate (HCO₃) and protons (H⁺). Bicarbonate may subsequently generate carbonate used in many functional activities by marine organisms. CAs play a crucial role in several physiological processes, e.g., respiration, inorganic carbon transport, intra and extra-cellular pH regulation, and bio-mineralization. Multiple transcript variants and protein isoforms exist in the organisms. Recently, 16 α-CA isoforms have been identified in the coral . Here, we focalized the interest on three coral isoforms: SpiCA1 and SpiCA2, localized in the coral-calcifying cells; and SpiCA3, expressed in the cytoplasm of the coral cell layers. The three recombinant enzymes were heterologously expressed and investigated for their inhibition profiles with sulfonamides and sulfamates. The three coral CA isoforms differ significantly in their susceptibility to inhibition with sulfonamides. This study provides new insights into the coral physiology and the comprehension of molecular mechanisms involved in the bio-mineralization processes, since CAs interact with bicarbonate transporters, accelerating the trans-membrane bicarbonate movement and modulating the pH at both sides of the plasma membranes.

摘要

碳酸酐酶(CAs,EC 4.2.1.1)是一种普遍存在的金属酶,负责 CO₂的可逆水合作用,生成碳酸氢盐(HCO₃)和质子(H⁺)。随后,碳酸氢盐可能会生成碳酸盐,被海洋生物用于许多功能活动。CAs 在多种生理过程中发挥着关键作用,例如呼吸、无机碳运输、细胞内外 pH 调节和生物矿化。在生物体中存在多种转录变体和蛋白质同工型。最近,在珊瑚中已经鉴定出 16 种 α-CA 同工型。在这里,我们关注三种珊瑚同工型:SpiCA1 和 SpiCA2,定位于珊瑚钙化细胞中;和 SpiCA3,在珊瑚细胞层的细胞质中表达。三种重组酶均进行了异源表达,并研究了它们与磺胺类和磺胺酸盐的抑制谱。三种珊瑚 CA 同工型对磺胺类药物的抑制敏感性有显著差异。这项研究为珊瑚生理学提供了新的见解,并深入了解生物矿化过程中涉及的分子机制,因为 CAs 与碳酸氢盐转运蛋白相互作用,加速跨膜碳酸氢盐的运动,并调节质膜两侧的 pH 值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bd/6471618/9120c351ecca/marinedrugs-17-00146-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bd/6471618/bcccd4ed5508/marinedrugs-17-00146-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bd/6471618/fb84b9254108/marinedrugs-17-00146-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bd/6471618/9120c351ecca/marinedrugs-17-00146-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bd/6471618/bcccd4ed5508/marinedrugs-17-00146-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bd/6471618/fb84b9254108/marinedrugs-17-00146-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7bd/6471618/9120c351ecca/marinedrugs-17-00146-g003.jpg

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