Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment
Butyrylcholinesterase (BChE) performs a significant function in Alzheimer’s disease progression. Experimental studies have shown that the function of BChE in the attenuation of cholinergic neurotransmission is essentially altered in brains of advanced AD patients. Here, using the complimentary metho...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022019016 |
| _version_ | 1828224236009816064 |
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| author | Sani Muhammad Uzairu Yahaya Tijani Madu Adamu Gadaka Babagana Modu Miriam Watafua Hadiza Ali Ahmad Umar Abdullahi Zakariya Aminu Ibrahim Aliyu Daja Hassan Zanna Abdullahi Balarabe Sallau |
| author_facet | Sani Muhammad Uzairu Yahaya Tijani Madu Adamu Gadaka Babagana Modu Miriam Watafua Hadiza Ali Ahmad Umar Abdullahi Zakariya Aminu Ibrahim Aliyu Daja Hassan Zanna Abdullahi Balarabe Sallau |
| author_sort | Sani Muhammad Uzairu |
| collection | DOAJ |
| description | Butyrylcholinesterase (BChE) performs a significant function in Alzheimer’s disease progression. Experimental studies have shown that the function of BChE in the attenuation of cholinergic neurotransmission is essentially altered in brains of advanced AD patients. Here, using the complimentary methods of enzyme kinetic studies, molecular modeling and protein-ligand interaction profiling, we sought to reveal the mechanistic and structural features of BChE-methyrosmarinate interactions. Molecular docking simulations revealed that methylrosmarinate dwelled well in the active centre of BChE, where it got involved in stabilizing non-covalent associations with myriad subsites. Enzyme kinetic experiments showed that the Vm and Ks values were 156.20 ± 3.11 U mg−1 protein and 0.13 ± 0.01 μM, respectively. The inhibition studies showed that methylrosmarinate apparently inhibited BChE in a linear mixed manner, with an IC50 value of 10.31 μM and a Ki value of 3.73 ± 1.52 μM. Taken together, the extremely reduced Ki value and the increased number of BChE–methylrosmarinate interactions presuppose that methylrosmarinate is a good inhibitor of BChE, despite the fact that the mechanism for the effect of BChE inhibition on several pathological conditions in vivo remains unexplored. |
| first_indexed | 2024-04-12T17:16:55Z |
| format | Article |
| id | doaj.art-8ced1b1314d34c759f75586a57ef101e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-12T17:16:55Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8ced1b1314d34c759f75586a57ef101e2022-12-22T03:23:37ZengElsevierHeliyon2405-84402022-09-0189e10613Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatmentSani Muhammad Uzairu0Yahaya Tijani1Madu Adamu Gadaka2Babagana Modu3Miriam Watafua4Hadiza Ali Ahmad5Umar Abdullahi Zakariya6Aminu Ibrahim7Aliyu Daja8Hassan Zanna9Abdullahi Balarabe Sallau10Department of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, Nigeria; Corresponding author.Department of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, NigeriaDepartment of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, NigeriaDepartment of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, NigeriaDepartment of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, NigeriaDepartment of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, NigeriaDepartment of Biochemistry, Federal University, Dutse, P. M. B. 7156 Dutse, NigeriaDepartment of Biochemistry, Bayero University, Kano, P.M.B. 30ll Kano, NigeriaDepartment of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, NigeriaDepartment of Biochemistry, University of Maiduguri, P.M.B. 1069 Maiduguri, NigeriaDepartment of Biochemistry, Ahmadu Bello University, Zaria, P.M.B. 1045 Zaria, NigeriaButyrylcholinesterase (BChE) performs a significant function in Alzheimer’s disease progression. Experimental studies have shown that the function of BChE in the attenuation of cholinergic neurotransmission is essentially altered in brains of advanced AD patients. Here, using the complimentary methods of enzyme kinetic studies, molecular modeling and protein-ligand interaction profiling, we sought to reveal the mechanistic and structural features of BChE-methyrosmarinate interactions. Molecular docking simulations revealed that methylrosmarinate dwelled well in the active centre of BChE, where it got involved in stabilizing non-covalent associations with myriad subsites. Enzyme kinetic experiments showed that the Vm and Ks values were 156.20 ± 3.11 U mg−1 protein and 0.13 ± 0.01 μM, respectively. The inhibition studies showed that methylrosmarinate apparently inhibited BChE in a linear mixed manner, with an IC50 value of 10.31 μM and a Ki value of 3.73 ± 1.52 μM. Taken together, the extremely reduced Ki value and the increased number of BChE–methylrosmarinate interactions presuppose that methylrosmarinate is a good inhibitor of BChE, despite the fact that the mechanism for the effect of BChE inhibition on several pathological conditions in vivo remains unexplored.http://www.sciencedirect.com/science/article/pii/S2405844022019016ButyrylcholinesteraseMethylrosmarinateEnzyme inhibitionEnzyme kineticsMolecular docking |
| spellingShingle | Sani Muhammad Uzairu Yahaya Tijani Madu Adamu Gadaka Babagana Modu Miriam Watafua Hadiza Ali Ahmad Umar Abdullahi Zakariya Aminu Ibrahim Aliyu Daja Hassan Zanna Abdullahi Balarabe Sallau Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment Heliyon Butyrylcholinesterase Methylrosmarinate Enzyme inhibition Enzyme kinetics Molecular docking |
| title | Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment |
| title_full | Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment |
| title_fullStr | Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment |
| title_full_unstemmed | Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment |
| title_short | Kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate: relevance to Alzheimer’s disease treatment |
| title_sort | kinetics and computational study of butyrylcholinesterase inhibition by methylrosmarinate relevance to alzheimer s disease treatment |
| topic | Butyrylcholinesterase Methylrosmarinate Enzyme inhibition Enzyme kinetics Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022019016 |
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