Evidence of human-like Ca2+ channels and effects of Ca2+ channel blockers in Acanthamoeba castellanii.,Chemical Biology & Drug Design

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Evidence of human-like Ca2+ channels and effects of Ca2+ channel blockers in Acanthamoeba castellanii.
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2019-01-29 , DOI: 10.1111/cbdd.13421
Abdul Mannan Baig ₁ , Zohaib Rana ₁ , Nuzair Waliani ₁ , Saiqa Karim ₁ , Mehdia Rajabali ₁

Affiliation

The evolution of voltage-gated calcium channel (Cav) in eukaryotes is an area of interest for biologists worldwide. The CLAN CL0030 and its family Ion_Trans 2 PF 07885 have been known to be present in prokaryotes, but the origin of these ion channels in Acanthamoeba spp. is yet to be determined. We inferred the origin of primitive forms of two-pore channels like proteins, human-like Cav 1.1 of L-type, and Cav subunit alpha-2/delta-1 in Acanthamoeba spp. early during evolution. By in-depth investigation into genomics, transcriptomics, use of bioinformatics tools and experimentations done with drugs like amlodipine and gabapentin on Acanthamoeba spp., we show the evidence of primitive forms of these channels in this protist pathogen. Genomics and transcriptomics of proteins ACA1_167020, 092610, and 270170 reflected their cellular expression in Acanthamoeba spp. We performed amino acid sequence homology, 3D structural modeling, ligand binding predictions, and dockings. Bioinformatics and 3D structural models show similarities between ACA1_167020, 092610, 270170, and different types of known human Cav. We show amoebicidal effects of amlodipine and gabapentin on Acanthamoeba spp., which can help design their structural analogs to target pathogenic genotypes of Acanthamoeba in diseases like Acanthamoeba keratitis and granulomatous amoebic encephalitis.

中文翻译：

棘形棘阿米巴中类似人的Ca2 +通道的证据和Ca2 +通道阻滞剂的作用。

真核生物中电压门控钙通道（Cav）的进化是全世界生物学家感兴趣的领域。已知CLAN CL0030及其家族Ion_Trans 2 PF 07885存在于原核生物中，但这些离子通道的起源是棘阿米巴属（Acanthamoeba spp）。尚未确定。我们推断原形的两孔通道的形式，如蛋白质，人类样的L型Cav 1.1和Acanthamoeba spp中的Cav亚基alpha-2 / delta-1。在进化的早期。通过对基因组学，转录组学，生物信息学工具的使用以及对诸如氨氯地平和加巴喷丁之类的药物在棘阿米巴属菌种上进行的实验的深入研究，我们证明了这种原生病原体中这些通道的原始形式的证据。蛋白质ACA1_167020、092610，270170和270170反映了它们在棘阿米巴菌种中的细胞表达。我们进行了氨基酸序列同源性，3D结构建模，配体结合预测和对接。生物信息学和3D结构模型显示了ACA1_167020、092610、270170和不同类型的已知人类Cav之间的相似性。我们显示了氨氯地平和加巴喷丁对棘阿米巴菌的杀菌作用，可以帮助设计其结构类似物，以靶向棘阿米巴的致病基因型，如棘阿米巴角膜炎和肉芽肿性阿米巴性脑炎。

更新日期：2019-01-29

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