Identification and characterization of sodium and chloride-dependent gamma-aminobutyric acid (GABA) transporters from eukaryotic pathogens as a potential drug target

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Abstract

We explored 285 completed eukaryotic pathogen genomes for GABA transporter proteins as effective chemotherapy targets. We identified 8 GABA proteins that spread across 4 phyla with 5 different pathogen species; Eimeria mitis Houghton, Neospora caninum Liverpool, S. mansoni, S. haematobium and Trichinella spiralis. Sub-cellular localization prediction revealed that these proteins are integral membrane and are mostly insoluble. It is found that about 81% of these proteins are non-crystallizable and 15% are crystallizable. Transmembrane helices predictions show that the GABA transporters have 10, 11, 12 and 14 TMHs with 15, 23, 31 and 11%, respectively. It is further observed that most of these GABA transporters are from several parasites`genomes.

Figures

  • Figure 1: Sodium and Chloride-dependent Gamma-aminobutyric Acid Transporters showing [A] crystallization propensity; about 15% and 81% of the proteins were predicted to be crystallizable and none-crystallizable respectively and [B] number of transmembrane helices, which shows that that the most of the GABA transporters have 10, 11, 12 and 14 TMHs with 15, 23, 31 and 11% respectively.
  • Figure 2: Phylogenetic tree of Sodium and Chloride-dependent Gamma-aminobutyric Acid Transporter proteins constructed using [A] Neighbor joining tree and [B] Maximum likelihood. In both phylogenetic tree methods, two of the three human GABA transporters are on the same minor clades, while all these proteins are on the same major clades with Bombyx mori GABA transporter and Bathymodiolus_septemdierum GABA transporter.
  • Figure 3: 2D Transmembrane helices of Sodium and Chloride-dependent Gamma-aminobutyric Acid Transporter proteins arranged side by side against phylogenetic tree.
  • Table 1: The Identified Sodium and Chloride-dependent Gamma-aminobutyric Acid (GABA) Transporters and their features
  • Table 2: Estimates of Pairwise Evolutionary Distance between Sequences.

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APA

Otarigho, B., & Falade, M. O. (2018). Identification and characterization of sodium and chloride-dependent gamma-aminobutyric acid (GABA) transporters from eukaryotic pathogens as a potential drug target. Bioinformation, 14(01), 021–030. https://doi.org/10.6026/97320630014021

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