Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study
Serine racemase (SR) catalyzes L-serine racemization to activate the N-methyl-D-aspartate receptor (NMDAR). NMDAR activation is associated with the progression of acute-to-chronic neuropathic pain. This study aimed to investigate NMDAR antagonist interactions with SR to obtain potential chronic pain...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Journal of Advanced Pharmaceutical Technology & Research |
| Subjects: | |
| Online Access: | http://www.japtr.org/article.asp?issn=2231-4040;year=2022;volume=13;issue=3;spage=232;epage=237;aulast=Laksono |
| _version_ | 1811295911903494144 |
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| author | Ristiawan Muji Laksono Handono Kalim Mohammad Saifur Rohman Nashi Widodo Muhammad Ramli Ahmad |
| author_facet | Ristiawan Muji Laksono Handono Kalim Mohammad Saifur Rohman Nashi Widodo Muhammad Ramli Ahmad |
| author_sort | Ristiawan Muji Laksono |
| collection | DOAJ |
| description | Serine racemase (SR) catalyzes L-serine racemization to activate the N-methyl-D-aspartate receptor (NMDAR). NMDAR activation is associated with the progression of acute-to-chronic neuropathic pain. This study aimed to investigate NMDAR antagonist interactions with SR to obtain potential chronic pain target therapy. Several NMDAR antagonist drugs were obtained from the drug bank, and malonate was used as a control inhibitor. Ligands were prepared using the open babel feature on PyRx. The SR structure was obtained from Protein data bank (PDB) (3l6B) and then docked with ligands using the AutoDock Vina. Haloperidol had a lower binding affinity than malonate and other ligands. Ethanol had the highest binding affinity than other drugs but could bind to the Adenosine triphosphate (ATP)-binding domain. Haloperidol is bound to reface that function for reprotonation in racemization reaction to produce D-serine. Halothane bond with Arg135 residues aligned negatively charged substrates to be reprotonated properly by reface. Tramadol is bound to amino acid residues in the triple serine loop, which determines the direction of the SR reaction. Several NMDAR antagonists such as haloperidol, halothane, ethanol, and tramadol bind to SR in the specific binding site. It reveals that SR potentially becomes an alternative target for chronic pain treatment. |
| first_indexed | 2024-04-13T05:40:39Z |
| format | Article |
| id | doaj.art-bb63ae63a2d3457b8971b448f4e1be44 |
| institution | Directory Open Access Journal |
| issn | 2231-4040 0976-2094 |
| language | English |
| last_indexed | 2024-04-13T05:40:39Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Advanced Pharmaceutical Technology & Research |
| spelling | doaj.art-bb63ae63a2d3457b8971b448f4e1be442022-12-22T03:00:08ZengWolters Kluwer Medknow PublicationsJournal of Advanced Pharmaceutical Technology & Research2231-40400976-20942022-01-0113323223710.4103/japtr.japtr_72_22Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking studyRistiawan Muji LaksonoHandono KalimMohammad Saifur RohmanNashi WidodoMuhammad Ramli AhmadSerine racemase (SR) catalyzes L-serine racemization to activate the N-methyl-D-aspartate receptor (NMDAR). NMDAR activation is associated with the progression of acute-to-chronic neuropathic pain. This study aimed to investigate NMDAR antagonist interactions with SR to obtain potential chronic pain target therapy. Several NMDAR antagonist drugs were obtained from the drug bank, and malonate was used as a control inhibitor. Ligands were prepared using the open babel feature on PyRx. The SR structure was obtained from Protein data bank (PDB) (3l6B) and then docked with ligands using the AutoDock Vina. Haloperidol had a lower binding affinity than malonate and other ligands. Ethanol had the highest binding affinity than other drugs but could bind to the Adenosine triphosphate (ATP)-binding domain. Haloperidol is bound to reface that function for reprotonation in racemization reaction to produce D-serine. Halothane bond with Arg135 residues aligned negatively charged substrates to be reprotonated properly by reface. Tramadol is bound to amino acid residues in the triple serine loop, which determines the direction of the SR reaction. Several NMDAR antagonists such as haloperidol, halothane, ethanol, and tramadol bind to SR in the specific binding site. It reveals that SR potentially becomes an alternative target for chronic pain treatment.http://www.japtr.org/article.asp?issn=2231-4040;year=2022;volume=13;issue=3;spage=232;epage=237;aulast=Laksonochronic painn-methyl-d-aspartate receptorserine racemasetreatment |
| spellingShingle | Ristiawan Muji Laksono Handono Kalim Mohammad Saifur Rohman Nashi Widodo Muhammad Ramli Ahmad Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study Journal of Advanced Pharmaceutical Technology & Research chronic pain n-methyl-d-aspartate receptor serine racemase treatment |
| title | Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study |
| title_full | Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study |
| title_fullStr | Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study |
| title_full_unstemmed | Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study |
| title_short | Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study |
| title_sort | serine racemase interaction with n methyl d aspartate receptors antagonist reveals potential alternative target of chronic pain treatment molecular docking study |
| topic | chronic pain n-methyl-d-aspartate receptor serine racemase treatment |
| url | http://www.japtr.org/article.asp?issn=2231-4040;year=2022;volume=13;issue=3;spage=232;epage=237;aulast=Laksono |
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