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Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Research Article

The Comparative Genomics and Network Analysis of eNOS by Using Different Bioinformatics Approaches

Author(s): Arpita Banerjee, Randeep Singh, Nymphaea Arora, Tania Arora, Vikash Prashar, Priya Godara, Arti Sharma*, Harish Changotra and Jyoti Parkash*

Volume 20, Issue 1, 2023

Published on: 15 February, 2023

Page: [37 - 56] Pages: 20

DOI: 10.2174/1875692120666230126110252

Price: $65

Abstract

Background: Nitric oxide synthase (NOS) is an enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine. It has three isoforms- (i) neuronal NOS (nNOS or NOS1), which participates in neural transmission; (ii) inducible NOS (iNOS or NOS2), which produces NO in macrophages; and (iii) endothelial NOS (eNOS or NOS3) that regulates blood pressure. The eNOS is mainly expressed in blood vessels and is a crucial regulator of endothelial homeostasis.

Objective: The present study aimed to unravel the role of eNOS in different signaling pathways and its involvement as a therapeutic target in various neurodegenerative disorders.

Methods: This study used various in silico methods for comprehensive genomic analysis of eNOS in 16 organisms from 7 different phyla. Prediction of conserved domains and evolutionary relationship for eNOS among 16 organisms was made. Various physical and chemical parameters, signal peptides, and transmembrane regions that helped understand its functional relevance were also studied.

Results: Three transcription factor binding sites (TFBS), i.e., CP2, AR, and LDSPOLYA, were identified in human eNOS, while ATF1, T3R, and STAT1 were predicted in mouse eNOS. Transcription factors were identified for each regulatory region in human as well as mouse eNOS. eNOS protein was predicted to harbor 14 different post-translational modification (PTM) sites, most of which have phosphorylation (serine followed by threonine and tyrosine phosphorylation) followed by sumoylation and palmitoylation among all the organisms used in the current study. However, human eNOS has a relatively lower number of PTM sites for tyrosine phosphorylation.

Conclusion: Structures of eNOS isoform, consistent with available biochemical and structural data, provide substantial insight into the NOS conformational changes, which give in-depth knowledge of the mechanism of eNOS, and will be helpful for better understanding the role of eNOS in pathophysiology.

Keywords: Nitric oxide synthase, nNOS, iNOS, eNOS, transcription factors, transcription factor binding sites, post-translational modification.

Graphical Abstract
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