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Tumor Discovery

ORIGINAL RESEARCH ARTICLE
Bioinformatics analysis of missense mutations

in CXCR1 implicates altered protein stability and
function

1
1†
1
Shah Kamal *, Amanullah Amanullah , Qingqing Wang , Najeeb Ullah ,
1†
3
2
Gohar Mushtaq *, Muhammad Nasir Iqbal , and Mohammad Amjad Kamal 4,5,6,7,8
1 Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing
Normal University, Nanjing, China
2 Department of Biochemistry, Center for Scientific Research, Faculty of Medicine, Idlib University,
Idlib, Syria
3 Department of Bioinformatics, Faculty of Biological and Chemical Sciences, The Islamia University
of Bahawalpur, Pakistan
4 Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care
Medicine and Institutes for Systems Genetics, West China School of Nursing, Frontiers Science
Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu,
China
5 King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
6 Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University,
Birulia, Savar, Dhaka, Bangladesh
7 Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of
Medical and Technical Sciences, Chennai, Tamil Nadu, India
8 Enzymoics, 7 Peterlee Place, Hebersham, NSW, Novel Global Community Educational Foundation,
† These authors contributed equally Australia
to this work.
*Corresponding authors:
Shah Kamal Abstract
(31183001@njnu.edu.cn)
Gohar Mushtaq Human CXCR1 is a G-protein α subunit i (Gαi)-coupled receptor (GPCR) that plays an
(dr.goher_mushtaq@idlib-university. important role in promoting leukocyte recruitment and activation in inflammatory regions;
com)
thus, its genetic contribution to human disorders warrants further investigation. In this
Citation: Kamal S, Amanullah A, study, we investigated whether oncogenic missense mutations in CXCR1 would affect its
Wang Q, et al. Bioinformatics
analysis of missense mutations in activity and hinder its ability to interact with its ligand. This study utilized a bioinformatics
CXCR1 implicates altered protein approach and employed precise and thorough computational methods to gain insights
stability and function. into the molecular characteristics of mutated CXCR1 that are responsible for causing
Tumor Discov. 2024;3(1):2512.
https://doi.org/10.36922/td.2512 diseases. I-TASSER was used to construct a mutant model with the required mutations.
Schrödinger’s Desmond software was used to evaluate how mutations affect the stability
Received: December 22, 2023 and function of proteins. In this study, 299 CXCR1 missense mutations were examined;
Accepted: February 21, 2024
Published Online: March 21, 2024 53 of these were reported to be disease-causing, five of which were directly associated
with cancer. The impact of the three cancer-causing mutations (N57D, R135C, and P302S)
Copyright: © 2024 Author(s).
This is an Open-Access article on protein stability and function was subsequently examined through computational
distributed under the terms of the analysis. Positions N57, R135, and P302 were determined to be highly conserved, and
Creative Commons Attribution substitutions with aspartic acid (D), cysteine (C), and serine (S), respectively, could impair
License, permitting distribution,
and reproduction in any medium, CXCR1 activity. Hence, our findings suggested that these mutations could alter CXCR1
provided the original work is ligand binding activity, lowering the risk of cancer and helping patients defend against
properly cited. pathogen invasion during a neutrophil-mediated innate immune response.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in Keywords: CXCR1; Molecular dynamic simulation; Molecular modeling; G protein-
published maps and institutional coupled receptors
affiliations.

Volume 3 Issue 1 (2024) 1 https://doi.org/10.36922/td.2512