In silico analysis of the inhibitory activities of GABA derivatives on 4-aminobutyrate transaminase

Iftikhar, Hira; Batool, Sidra; Deep, Aakash; Narasimhan, Balasubramanian; Sharma, Prabodh Chander; Malhotra, Manav

doi:10.1016/j.arabjc.2013.03.007

Cited by 12 publications

(17 citation statements)

References 22 publications

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“…Dopamine N-acetyltransferase-like is a kind of N-acetyltransferase to catalyze the N-acetylation of dopamine into N- acetyldopamine, which is the major precursor for quinone and subsequent pigment (Noh et al, 2016). 4-aminobutyrate aminotransferase (ABAT) catalyzes the first step of the principal inhibitory neurotransmitter γ-aminobytyric acid (GABA) to degrade within the mitochondrial matrix (Iftikhar et al, 2017). Moreover, GABA has been implicated in modulating the opioid mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Digital gene expression analysis in the gills of Ruditapes philippinarum exposed to short- and long-term exposures of ammonia nitrogen

Cong

Cao

et al. 2018

Aquatic Toxicology

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Previous study revealed severe toxic effects of ammonia nitrogen on Ruditapes philippinarum including lysosomal instability, disturbed metabolic profiles, gill tissues with damaged structure, and variation of neurotransmitter concentrations. However, the underlying molecular mechanism was not fully understood yet. In the present study, digital gene expression technology (DGE) was applied to globally screen the key genes and pathways involved in the responses to short- and long-term exposures of ammonia nitrogen. Results of DGE analysis indicated that short-term duration of ammonia exposure affected pathways in Dorso-ventral axis formation, Notch signaling, thyroid hormone signaling and protein processing in endoplasmic reticulum. The long-term exposure led to DEGs significantly enriched in gap junction, immunity, signal and hormone transduction, as well as key substance metabolism pathways. Functional research of significantly changed DEGs suggested that the immunity of R. philippinarum was weakened heavily by toxic effects of ammonia nitrogen, as well as neuro-transduction and metabolism of important substances. Taken together, the present study provides a molecular support for the previous results of the detrimental toxicity of ammonia exposure in R. philippinarum, further work will be performed to investigate the specific genes and their certain functions involved in ammonia toxicity to molluscs.

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Section: Discussionmentioning

confidence: 99%

Digital gene expression analysis in the gills of Ruditapes philippinarum exposed to short- and long-term exposures of ammonia nitrogen

Cong

Cao

et al. 2018

Aquatic Toxicology

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“…In docking analysis, Compound 5a indicated higher binding affinity with docking score of À11.9 kcal/mol against GABA AT than other co-ligands. From the docking analysis, we realized that the binding scores generated were found to be better than the one proposed by another researcher [39]. The physicochemical descriptors used in QSAR analysis (model 1) in this study were important parameters to consider in improving the potency of these substituted quinoxalines and thiadiazoles derivatives as inhibitors of GABA AT .…”

Section: Resultsmentioning

confidence: 74%

Molecular docking and QSAR analysis of a few Gama amino butyric acid aminotransferase inhibitors

Abdulfatai

Uzairu²,

Shallangwa³

2018

Egyptian Journal of Basic and Applied Sciences

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Molecular docking and quantitative structure-activity relationship (QSAR) studies were carried out on 37 anticonvulsant compounds to develop a robust model for the prediction of anticonvulsant activities against Gama amino butyric acid aminotransferase (GABA AT) and to determine the dominant structural amino acid residues responsible for the binding affinity of the ligand-GABA AT complex. AutoDock Vina of PyRx virtual screening software was used to perform the molecular docking while Genetic function algorithm (GFA) was used to select the descriptors and to generate the correlation models that relate the structural features to the biological activities. The best binding affinity was found to be À11.9 Kcal/mol (compound 5a) while best QSAR model (model 1) was obtained with R 2 of 0.970192, an R 2 adj value of 0.963095, Q 2 LOO value of 0.947995 and R 2 pred of 0.813. These confirms the stability, reliability, robustness and predictability of the model. Our research has shown that the binding affinity generated was found to be better than the one reported by another researcher. And the high correlation coefficient, (R 2) shows that the model was reliable, robust and predictable. Our QSAR model and molecular docking results corroborate with each other (most especially in the area of binding affinity and atomic electronegativity of the inhibitors) and propose the directions for the design of new inhibitors with better activity against an enzyme that is responsible for epilepsy (GABAAT).

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“…The ligand was docked deeply within the binding pocket region forming a hydrogen bond with Gly440 (3.04 Å), and hydrophobic interactions with Cys439, Asn423, Arg422, His44, Arg430, Leu436, Ile426, Tyr438, Ile72, Tyr69, His206, Gly438, Lys203, and Glu270. From the docking analysis, we realized that the binding scores generated were found to be better than the one proposed by other researcher [28].…”

Section: Discussionmentioning

confidence: 75%

Quantitative structure-activity relationship and molecular docking studies of a series of quinazolinonyl analogues as inhibitors of gamma amino butyric acid aminotransferase

Abdulfatai

Uzairu

Shallangwa

2017

Journal of Advanced Research

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In silico analysis of the inhibitory activities of GABA derivatives on 4-aminobutyrate transaminase

Cited by 12 publications

References 22 publications

Digital gene expression analysis in the gills of Ruditapes philippinarum exposed to short- and long-term exposures of ammonia nitrogen

Digital gene expression analysis in the gills of Ruditapes philippinarum exposed to short- and long-term exposures of ammonia nitrogen

Molecular docking and QSAR analysis of a few Gama amino butyric acid aminotransferase inhibitors

Quantitative structure-activity relationship and molecular docking studies of a series of quinazolinonyl analogues as inhibitors of gamma amino butyric acid aminotransferase

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