Identification of Unique Water Molecules in Human GRK2 Protein with Bound and Unbound GβGγ Subunit: A Study by Structural Bioinformatics Method
Journal Title: International Journal of Bioinformatics and Intelligent Computing - Year 2023, Vol 2, Issue 2
Abstract
The human G-protein coupled receptor kinase 2 (hGRK2) regulates the desensitization of beta-adrenergic receptors (β-AR), and its overexpression has been implicated in heart failure. The hGRK2 is a serine/ threonine kinase and is one of the members of the AGC family, and it contains the four domains (i) RGS or RH domain (regulator of G-protein signaling res. id. 54-175), (ii) protein kinase or CAT domain (res. id. 191-453), (iii) AGC Kinase domain (res. Id 454-521), and (iv) PH domain (Pleckstrin homology, res. Id. 558-652). Present computational investigations on multiple analyses of X-ray structures (bound and unbound conformation of GβGγ) highlight the presence of seventeen unique water molecules (W1 to W17) that are only available either in hGRK2 with GβGγ or without GβGγ. These water molecules are subdivided into category-I (W1 to W8), which is observed with unbound GβGγ conformation, and category-II (W9 to W17) in hGRK2 with bound GβGγ conformation. The MD simulation results suggest the non-crystal and crystal water molecules are inaccessible to reaching W3, W10, and W12 water sites because they are deeply buried and shielded by neighboring residues, whereas W9, W11, and W13 are accessible by crystal water in MD simulation but not allow entering non-crystal or MD water molecules. During the structural transition of hGRK2 from unbound to bound hGβGγ state, water molecules of category-I (W1 to W8) departed from their respective domains, and water molecules of Category-II (W9 to W17) were reached simultaneously during unbound to bound GβGγ conformation. In this context, the present work identifies new biochemical insights to highlight some rationale clues for heart disease.
Authors and Affiliations
Hridoy Ranjan Bairagya, Sayanti Pal, Sabarno Baral
Keywords
Related Articles
- EP ID EP724412
- DOI https://doi.org/10.61797/ijbic.v2i2.242
- Views 21
- Downloads 0
Natural Language Processing – Finding the Missing Link for Oncologic Data, 2022
Oncology like most medical specialties, is undergoing a data revolution at the center of which lie vast and growing amounts of clinical data in unstructured, semi-structured and structed formats. Artificial intelligence...
Deep Learning to Predicting Live Births and Aneuploid Miscarriages from Images of Blastocysts Combined with Maternal Age
Objectives: Making an artificial intelligence (AI) classifier that uses the maternal age and an image of the implanted blastocyst to determine the probability of getting a live birth. Methods: The dataset comprised m...
A Scalable Algorithm for Interpreting DNA Sequence and Predicting the Response of Killer T-Cells in Systemic Lupus Erythematosus Patients
The incidence and prevalence of SLE in North America are 23.2 and 241 per 100,000 people per year respectively while the incidence in Africa is 0.3 per 100,000 people per year. The study aims to predict the autoimmune re...
Facial Skin Disease Detection using Image Processing
Busy lifestyle, modernization, increasing pollution and unhealthy diet have led to problems which people are neglecting. Not drinking enough water, stress and hormonal changes are causing problems to skin. Causes may be...
Review of Bioinformatics Tools and Techniques to Accelerate Ovarian Cancer Research
Since the history of humans there was no definitive cure for cancer. The rapid development in the field of bioinformatics has resulted in acceleration of advancement of cancer research. As computing and IT technology imp...