In-silico analysis reveals druggable single nucleotide polymorphisms in angiotensin 1 converting enzyme involved in the onset of blood pressure

Brenda Udosen; Opeyemi Soremekun; Chinwe Ekenna; Olaposi Idowu Omotuyi; Tinashe Chikowore; Oyekanmi Nashiru; Segun Fatumo

doi:10.1186/s13104-021-05879-z

In-silico analysis reveals druggable single nucleotide polymorphisms in angiotensin 1 converting enzyme involved in the onset of blood pressure

BMC Res Notes. 2021 Dec 20;14(1):457. doi: 10.1186/s13104-021-05879-z.

Authors

Brenda Udosen^{1

2

3}, Opeyemi Soremekun¹, Chinwe Ekenna⁴, Olaposi Idowu Omotuyi⁵, Tinashe Chikowore^{6

7}, Oyekanmi Nashiru³, Segun Fatumo^{8

9

10}

Affiliations

¹ The African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda.
² The African Center of Excellence in Bioinformatics of Bamako (ACE-B), University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
³ H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria.
⁴ University at Albany, Albany, NY, USA.
⁵ Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.
⁶ Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁷ MRC/Wits Developmental Pathways for Health Research Unit, Department of Pediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁸ The African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda. segun.fatumo@lshtm.ac.uk.
⁹ H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria. segun.fatumo@lshtm.ac.uk.
¹⁰ Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. segun.fatumo@lshtm.ac.uk.

Abstract

Objective: The Angiotensin 1 converting enzyme (ACE1) gene plays a critical role in regulating blood pressure and thus, it has become a major therapeutic target of antihypertensives. Single nucleotide polymorphisms (SNPs) occurring within a gene most especially at the functional segment of the genes alter the structure-function relationship of that gene.

Results: Our study revealed that five nsSNPs of the ACE1 gene were found to be potentially deleterious and damaging and they include rs2229839, rs14507892, rs12709442, and rs4977 at point mutations P351R, R953Q, I1018T, F1051V, and T1187M. The protein stability predictive tools revealed that all the nsSNPs decreased stability of the protein and the Consurf server which estimates the evolutionary conservation profile of a protein showed that three mutants were in the highly conserved region. In conclusion, this study predicted potential druggable deleterious mutants that can be further explored to understand the pathological basis of cardiovascular disease.

Keywords: Angiotensin-Converting enzyme 1; Blood Pressure; SNP informatics; Single-nucleotide polymorphisms.

MeSH terms

Blood Pressure
Humans
Hypertension / genetics*
Peptidyl-Dipeptidase A / genetics*
Polymorphism, Single Nucleotide*
Proteins

Substances

Proteins
ACE protein, human
Peptidyl-Dipeptidase A

Abstract

MeSH terms

Substances

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