Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study

Ristiawan Muji Laksono; Handono Kalim; Mohammad Saifur Rohman; Nashi Widodo; Muhammad Ramli Ahmad

doi:10.4103/japtr.japtr_72_22

Users Online: 1260

ORIGINAL ARTICLE

Year : 2022 | Volume : 13 | Issue : 3 | Page : 232-237

Serine racemase interaction with N-methyl-D-aspartate receptors antagonist reveals potential alternative target of chronic pain treatment: Molecular docking study

Ristiawan Muji Laksono¹, Handono Kalim², Mohammad Saifur Rohman³, Nashi Widodo⁴, Muhammad Ramli Ahmad⁵
¹ Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Brawijaya University/Dr. Saiful Anwar General Hospital, Malang, Indonesia
² Department of Internal Medicine, Faculty of Medicine, Brawijaya University/Dr Saiful Anwar General Hospital, Malang, Indonesia
³ Department of Cardiology and Vascular Medicine, Faculty of Medicine, Brawijaya University/Dr Saiful Anwar General Hospital, Malang, Indonesia
⁴ Department of Biology, Faculty of Mathematics and Natural Science, Brawijaya University, Malang, Indonesia
⁵ Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Correspondence Address:
Dr. Ristiawan Muji Laksono
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Brawijaya University/Dr. Saiful Anwar Malang, Jl. Jaksa Agung Suprapto no. 2 Malang, East Java
Indonesia

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/japtr.japtr_72_22

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.

[FULL TEXT] [PDF]*

Table of Contents

Similar in PUBMED

Search Pubmed for

Search in Google Scholar for

Related articles

Citation Manager

Access Statistics

Reader Comments

Email Alert *

Add to My List *

* Requires registration (Free)

Article Access Statistics

Viewed	218

Printed	0

Emailed	0

PDF Downloaded	32

Comments	[Add]