Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
The Role of Aminotransferase in Human Health and Disease
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

The Role of Aminotransferase in Human Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 3030

Special Issue Editors

Dr. Barbara Cellini

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy
Interests: rare disorders; vitamin B6; protein folding; pharmacological chaperones; enzyme administration; hyperoxaluria
Dr. Silvia Grottelli

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy
Interests: rare disorders; vitamin B6; protein folding; pharmacological chaperones; enzyme administration; hyperoxaluria
Dr. Leonardo Gatticchi

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy
Interests: rare disorders; vitamin B6; protein folding; pharmacological chaperones; enzyme administration; hyperoxaluria

Special Issue Information

Dear Colleagues,

Aminotransferases (ATs) are enzymes that catalyze the interconversion of amino acids and α-keto acids. Their importance is primarily related to the metabolism of amino acids, as both the energy source and components of synthesized proteins. Transamination reactions also play a crucial role in the synthesis of bioactive compounds, as well as in the degradation of potentially toxic metabolic products. In addition, thanks to their capability of introducing amino groups into ketones or keto acids, ATs have useful applications in the chemical industry. Finally, serum levels of specific transaminases in the blood represent a biomarker for the diagnosis and prognosis of many diseases.

Papers related to any molecular aspect of ATs role in human health and disease, will be considered for this Special Issue. Experimental and bioinformatics papers, up-to-date review articles, and commentaries are also welcome.

Dr. Barbara Cellini
Dr. Silvia Grottelli 
Dr. Leonardo Gatticchi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • aminotransferases
  • pyridoxal phosphate
  • biomarkers
  • rare diseases

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

17 pages, 8923 KiB  
Article
Discovery of GABA Aminotransferase Inhibitors via Molecular Docking, Molecular Dynamic Simulation, and Biological Evaluation
by Muhammad Yasir, Jinyoung Park, Yuno Lee, Eun-Taek Han, Won Sun Park, Jin-Hee Han, Yong-Soo Kwon, Hee-Jae Lee and Wanjoo Chun
Int. J. Mol. Sci. 2023, 24(23), 16990; https://doi.org/10.3390/ijms242316990 - 30 Nov 2023
Cited by 2 | Viewed by 1172
Abstract
γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that degrades γ-aminobutyric (GABA) in the brain. GABA is an important inhibitory neurotransmitter that plays important neurological roles in the brain. Therefore, GABA-AT is an important drug target that regulates GABA levels. Novel [...] Read more.
γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that degrades γ-aminobutyric (GABA) in the brain. GABA is an important inhibitory neurotransmitter that plays important neurological roles in the brain. Therefore, GABA-AT is an important drug target that regulates GABA levels. Novel and potent drug development to inhibit GABA-AT is still a very challenging task. In this study, we aimed to devise novel and potent inhibitors against GABA-AT using computer-aided drug design (CADD) tools. Since the crystal structure of human GABA-AT was not yet available, we utilized a homologous structure derived from our previously published paper. To identify highly potent compounds relative to vigabatrin, an FDA-approved drug against human GABA-AT, we developed a pharmacophore analysis protocol for 530,000 Korea Chemical Bank (KCB) compounds and selected the top 50 compounds for further screening. Preliminary biological analysis was carried out for these 50 compounds and 16 compounds were further assessed. Subsequently, molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations were carried out. In the results, four predicted compounds, A07, B07, D08, and H08, were found to be highly potent and were further evaluated by a biological activity assay to confirm the results of the GABA-AT activity inhibition assay. Full article
(This article belongs to the Special Issue The Role of Aminotransferase in Human Health and Disease)
►▼ Show Figures

Figure 1

15 pages, 3558 KiB  
Article
Computational Exploration of the Effects of Mutations on GABA Aminotransferase in GABA Aminotransferase Deficiency
by Muhammad Yasir, Jinyoung Park, Eun-Taek Han, Won Sun Park, Jin-Hee Han, Yong-Soo Kwon, Hee-Jae Lee and Wanjoo Chun
Int. J. Mol. Sci. 2023, 24(13), 10933; https://doi.org/10.3390/ijms241310933 - 30 Jun 2023
Cited by 3 | Viewed by 1486
Abstract
Gamma-aminobutyric acid (GABA) transaminase—also called GABA aminotransferase (GABA-AT)—deficiency is a rare autosomal recessive disorder characterized by a severe neonatal-infantile epileptic encephalopathy with symptoms such as seizures, hypotonia, hyperreflexia, developmental delay, and growth acceleration. GABA transaminase deficiency is caused by mutations in GABA-AT, the [...] Read more.
Gamma-aminobutyric acid (GABA) transaminase—also called GABA aminotransferase (GABA-AT)—deficiency is a rare autosomal recessive disorder characterized by a severe neonatal-infantile epileptic encephalopathy with symptoms such as seizures, hypotonia, hyperreflexia, developmental delay, and growth acceleration. GABA transaminase deficiency is caused by mutations in GABA-AT, the enzyme responsible for the catabolism of GABA. Mutations in multiple locations on GABA-AT have been reported and their locations have been shown to influence the onset of the disease and the severity of symptoms. We examined how GABA-AT mutations influence the structural stability of the enzyme and GABA-binding affinity using computational methodologies such as molecular dynamics simulation and binding free energy calculation to understand the underlying mechanism through which GABA-AT mutations cause GABA-AT deficiency. GABA-AT 3D model depiction was carried out together with seven individual mutated models of GABA-AT. The structural stability of all the predicted models was analyzed using several tools and web servers. All models were evaluated based on their phytochemical values. Additionally, 100 ns MD simulation was carried out and the mutated models were evaluated using RMSD, RMSF, Rg, and SASA. gmxMMPBSA free energy calculation was carried out. Moreover, RMSD and free energy calculations were also compared with those obtained using online web servers. Our study demonstrates that P152S, Q296H, and R92Q play a more critical role in the structural instability of GABA-AT compared with the other mutated models: G465R, L211F, L478P, and R220K. Full article
(This article belongs to the Special Issue The Role of Aminotransferase in Human Health and Disease)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop