Scholarlink

Purpose <p>Steroid 5α-reductase type-2 (SRD5A2) enzyme converts testosterone into dihydrotestosterone (DHT), an androgen implicated in prostate cancer (PCa) progression. This study aimed to investigate the impact of A49T polymorphism on the binding efficiency of commonly occurring phytosterols, standard of care medication and SRD5A2 endogenous ligand in comparison to the wild-type.</p> Methods <p>Homology modelling, protein structure analysis, molecular docking, and molecular dynamics simulation were employed for in silico evaluation.</p> Results <p>The structural comparison showed A49T polymorphism conferred wholesome changes to the root mean square fluctuation (RMSF), root mean square deviation (RMSD), and contact maps of SRD5A2 wild-type. The molecular docking study also revealed SRD5A2 polymorphism increased the binding efficiency of the phytosterols and clinical inhibitors compared to the wild-type. The molecular dynamics simulation of both SRD5A2 wild-type and A49T variant complexes with stigmasterol was stable with strong interaction between the ligand and the proteins. However, the mutation influenced the initial conformational accommodation of the ligand.</p> Conclusion <p>In light of this findings, the A49T variant introduces modest but potentially significant alterations in protein structure, flexibility, binding affinities and interacting residue profiles compared to the wild-type depite this polymorphism not occuring in the enzyme's binding site. The effects of this mutation on SRD5A2 dynamics and binding characteristics of these phytosterols may have implications for pharmacological targeting of SRD5A2 in PCa, particularly in A49T SNP carriers.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Steroid 5α-Reductase 2 Single Nucleotide Polymorphism Modulation of Phytosterol Binding Efficiency: An In silico Approach

  • 期刊论文

  • 发表日期：

    2025年9月9日

查看全文
  • Franklyn Nonso Iheagwam,
  • Timothy Oluwatimileyin Ayeni,
  • Shalom Nwodo Chinedu

摘要

Purpose

Steroid 5α-reductase type-2 (SRD5A2) enzyme converts testosterone into dihydrotestosterone (DHT), an androgen implicated in prostate cancer (PCa) progression. This study aimed to investigate the impact of A49T polymorphism on the binding efficiency of commonly occurring phytosterols, standard of care medication and SRD5A2 endogenous ligand in comparison to the wild-type.

Methods

Homology modelling, protein structure analysis, molecular docking, and molecular dynamics simulation were employed for in silico evaluation.

Results

The structural comparison showed A49T polymorphism conferred wholesome changes to the root mean square fluctuation (RMSF), root mean square deviation (RMSD), and contact maps of SRD5A2 wild-type. The molecular docking study also revealed SRD5A2 polymorphism increased the binding efficiency of the phytosterols and clinical inhibitors compared to the wild-type. The molecular dynamics simulation of both SRD5A2 wild-type and A49T variant complexes with stigmasterol was stable with strong interaction between the ligand and the proteins. However, the mutation influenced the initial conformational accommodation of the ligand.

Conclusion

In light of this findings, the A49T variant introduces modest but potentially significant alterations in protein structure, flexibility, binding affinities and interacting residue profiles compared to the wild-type depite this polymorphism not occuring in the enzyme's binding site. The effects of this mutation on SRD5A2 dynamics and binding characteristics of these phytosterols may have implications for pharmacological targeting of SRD5A2 in PCa, particularly in A49T SNP carriers.