Résumé d'article de jounal
Effect of Amino Acid Substitutions in OR9K2 on the Olfactory Neural Response activating Odor Molecules

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Détails sur la publication
Liste des auteurs: Wejdan Mohammed AlGhamdi, Hind Saleh Alsuwat, Noor B Almandil, Abdulla AlSulaiman, J. Francis Borgio. and Sayed AbdulAzeez
Editeur: Medknow Publications
Année de publication: 2021
Journal: Saudi Journal of Medicine and Medical Sciences
Lexique des acronymes: SJMMS
Numéro du volume: 9
Numéro de publication: 1
Page d'accueil: 92
Dernière page: 92
Nombre de pages: 1
ISSN: 1658-631X
Web of Science ID:
Scopus ID:
eISSN: 2321-4856

Background: Olfactory receptors (ORs) are expressed mainly in the sensory neurons, OR9K2 is an olfactory receptor, which is located in the nose specifically on the plasma membrane. The main role of OR9K2 is to initiate neuronal response and odorant signals.

Objectives: The purpose of the study is to identify the amino acid substitution in OR9K2 that make the protein more favourable for odour molecules, which might help in early diagnosis and drug design.

Methods and Material: Using in silico tools, the study focused on selecting the most pathogenic amino acid substitution of OR9K2 gene, based on the data retrieved from NCBI and previously identified prevalent non-synonymous SNPs (nsSNP) in Saudis using microarray analysis. The study also continues to collect nsSNPs (non-synonymous) of Saudi autistic patients using DNA sequencing. OR 9K2 (PDB ID: 6tp3.1.A) protein was homology modeled and validated using PROCHECK. Mutated OR9K2 proteins were generated using SwissPDB and undergo Protein – odour molecule interaction using molecular operating environment. Ten odor molecules were selected that are widely used in Arabian Gulf regions. All the selected odor molecules were docked against the wild and mutated proteins.

Results and Discussion: Of 463 nsSNPs, 12 most pathogenic nsSNPs were selected based on the cumulative score generated using nine bioinformatics tools and two more nsSNPs that are prevalent among Saudis were added. Thirty percent (Anisole, Piperonylacetone, delta-Guaiene) of the selected molecules did not interact with the wild OR9K2, interacted with the mutated OR9K2. Sanger sequence analysis revealed a frameshift mutation in the Saudi population.

Conclusions: Interaction of odor molecule with mutant, but not wild, OR9K2 indicates that normal protein cannot activate the neural response of olfactory receptors, while the mutated protein (L285R) can activate ORs.

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Dernière mise à jour le 2021-24-08 à 10:24