PUBLICATION
Characterization, Docking and Molecular Dynamics Simulation of Gonadotropin-Inhibitory Hormone Receptor (GnIHR2) in Labeo Catla
- Authors
- Kumar, P., Kumar, M., Wisdom, K.S., Pathakota, G.B., Nayak, S.K., Reang, D., Nagpure, N.S., Sharma, R.
- ID
- ZDB-PUB-200902-10
- Date
- 2020
- Source
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 54: 825-841 (Journal)
- Registered Authors
- Keywords
- Labeo catla; Reproduction; RF313; Molecular docking; MD simulation
- MeSH Terms
-
- Amino Acid Sequence/genetics
- Animals
- Carps/genetics
- Gonadotropin-Releasing Hormone/genetics
- Gonadotropins/metabolism
- Hypothalamic Hormones/metabolism*
- Molecular Dynamics Simulation
- Phylogeny
- Piperidines/pharmacology
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism
- Receptors, Neuropeptide/genetics*
- Receptors, Neuropeptide/metabolism
- Valine/analogs & derivatives
- Valine/pharmacology
- PubMed
- 32871065 Full text @ Cell Physiol. Biochem.
Citation
Kumar, P., Kumar, M., Wisdom, K.S., Pathakota, G.B., Nayak, S.K., Reang, D., Nagpure, N.S., Sharma, R. (2020) Characterization, Docking and Molecular Dynamics Simulation of Gonadotropin-Inhibitory Hormone Receptor (GnIHR2) in Labeo Catla. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 54:825-841.
Abstract
Background/aims GnIH receptors (GnIHRs) belong to the family of G-protein coupled receptors (GPCRs) and play a key role in the regulation of reproduction from fishes to mammals, either by inhibiting or stimulating the expression of gonadotropins. The aim of this study was to characterize GnIH receptor (GnIHR2) from Indian Major Carp, Labeo catla and its docking and simulation with GnIH antagonist RF313.
Methods The full length sequence of GnIHR2 was obtained with RACE PCR. The docking analysis of RF313 with GnIHR2 receptor was performed with AutoDock v. 4.2.6 and molecular dynamics (MD) simulation with GROMACS 5.0.
Results In the present study, we cloned full-length cDNA (1733 bp) of GnIHR2 from the brain of L. catla. The phylogenetic analysis showed clustering of catla GnIHR2 with goldfish and zebrafish in the GPR147 group. L. catla GnIHR2 receptor comprised seven transmembrane domains and the 3D-structure was predicted by I-TASSER tool. The docking analysis revealed high binding affinity (-11.6 kcal/mol) of GnIH antagonist, RF313 towards GnIHR2 receptor. The primary bonds involved were alkyl and hydrogen bonds while the amino acids participated were proline 43, 210, 339, cysteine 214, leucine 211, serine 213 and phenylalanine 338. The MD simulation analysis of docked complex for 100 nano-seconds (ns) in the lipid membrane environment showed the stability of the complex with time.
Conclusion Our study showed that GnIH antagonist, RF313 interact tightly with the GnIH receptor, GnIHR2 of L. catla. To the best of our knowledge, this is the first report on computational modelling and MD simulation of GnIH receptor in fishes. This will help in functional characterization studies of GnIH/GnIHR system in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping