Possible inhibition mechanism of dobutamine hydrochloride as potent inhibitor for human glucose-6-phosphate dehydrogenase enzyme. Issue 1 (2nd January 2022)

• Record Type: Journal Article
• Authors: Kizilbay, Gokce; Karaman, Muhammet
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 1(2022)
• Page Start: 204
• Page End: 212
• Publication Date: 2022-01-02
• Subjects: Antiarrhythmic drugs -- glucose-6-phosphate dehydrogenase -- allosteric modulation -- in vitro -- in silico; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2020.1811155
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: Glucose-6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme in the pentose phosphate pathway. One of the enzyme's most important functions is the production of a reducing agent that is essential for preserving the level of reduced glutathione (GSH). However, some chemicals, such as industrial waste and the active ingredients of several drugs, can cause reduction or blockage in this enzyme's activity. This case causes the occurrence of anemia by damaging erythrocytes. In this study, the G6PD enzyme was purified 21, 981 fold with affinity chromatography and the effects of the active ingredients of some antiarrhythmic drugs on enzyme activity were investigated with in vitro and in silico methods. We found that dobutamine hydrochloride significantly decreased enzyme activity and its inhibitory constant ( Ki ) value was calculated as 19.02 ± 4.83 mM. The in vitro study results also show that dobutamine hydrochloride is a potent inhibitor of enzyme activity. We also found that dobutamine hydrochloride inhibits the hG6PD enzyme's activity by causing structural alterations in substrate and coenzyme binding sites. Communicated by Ramaswamy H. Sarma