Evidence of human‐like Ca2+ channels and effects of Ca2+ channel blockers in Acanthamoeba castellanii. (29th January 2019)

• Record Type: Journal Article
• Authors: Baig, Abdul Mannan; Rana, Zohaib; Waliani, Nuzair; Karim, Saiqa; Rajabali, Mehdia
• Is Part Of: Chemical biology & drug design. Volume 93:Number 3(2019)
• Page Start: 351
• Page End: 363
• Publication Date: 2019-01-29
• Subjects: Acanthamoeba castellanii -- amlodipine -- amoebicidal -- bioinformatics tools -- docking drugs -- Eukaryotic ion channels -- free‐living amoebae -- voltage‐gated calcium channels structural modeling; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13421
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract: 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. Abstract : We show that human Ca channels had their origins in primitive unicellular eukaryotes like Acanthamoeba spp. that have homology with their human counterparts. Bioinformatics, 3D structural modelling, and docking show that Ca channels like proteins in Acanthamoeba have homology with their human counterparts. Amlodipine and gabapentin show amoebicidal effects in Acanthamoeba. Structural analogs of these drugs can help in the treatment of fatal encephalitis and keratitis caused by Acanthamoeba spp.