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Structural Insights into Mouse Beta3 Adrenergic Receptor: A Homology Modeling Study
  • Asha Abraham,
  • Vijayalakshmi Gangadhara
Asha Abraham
St Aloysius College

Corresponding Author:[email protected]

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Vijayalakshmi Gangadhara
St Aloysius College
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Abstract

Background: The β3 adrenergic receptor (AR) plays a crucial role in regulating lipolysis and thermogenesis in visceral adipose tissue and is an important drug development target for obesity and diabetes. However, there is no structural information available for the mouse β3 AR, and its selectivity mechanism is poorly understood. Objective: To address this, the study aimed to construct and validate a 3D homology model of the mouse β3 AR using computational methods and multiple software tools. Methods: we constructed and validated a 3D homology model of the mouse β3 AR using the β3 ADR amino acid sequence of Mus musculus from NCBI and identified possible templates using protein BLAST. We characterized the protein and aligned the sequence with Clustal Omega to identify conserved regions. The homology model was constructed using three different software/servers: SWISS Model, Phyre2.0, and iTASSER, and validated using various techniques. Results: The β3 AR model comprises 400 amino acid residues, exhibits a theoretical pI of 9.57, instability index of 0.57, aliphatic index of 98.35, and GRAVY value of 0.289. Phyre2.0 constructed the most accurate β3 AR model using c2rh1A as a template, with an ERRAT score of 84.076. The Ramachandran plot revealed 93.2% of residues in the favored regions. Conclusion: The study highlights the significance of homology modeling as a computational method for predicting protein 3D structure and emphasizes the importance of comparing and evaluating models generated from multiple templates and software tools. The β3 AR model generated in this study may facilitate future research on the structure and function of the β3 AR, potentially leading to the development of more effective drugs for obesity and diabetes.