Bioinformatic Analysis of the Hawthorn PAL gene's Role in OPC Biosynthesis and its Sstructural Comparison to the Cardiomyopathy Gene MYBPC3

Forghani, Seyed Ali; Rashki Ghalehnoo, Sara; Shafiei, Yeganeh; Fazeli-Nasab, Bahman

doi:10.22034/jmpb.2025.370886.2064

Bioinformatic Analysis of the Hawthorn PAL gene's Role in OPC Biosynthesis and its Sstructural Comparison to the Cardiomyopathy Gene MYBPC3

Articles in Press

Document Type : Research Paper

Authors

¹ Student Research Committee, Zabol University of Medical Sciences, Zabol, Iran

² Department of Cardiology, School of Medicine, Amir al momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran

³ Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

⁴ Department of Agronomy and Plant Breeding, Agriculture Institute, Research Institute of Zabol, Zabol, Iran

10.22034/jmpb.2025.370886.2064

Abstract

This investigation conducted a computational examination of the phenylalanine ammonia-lyase (PAL) gene within Crataegus species, a pivotal enzyme governing the phenylpropanoid pathway and the biosynthesis of phenolic and flavonoid metabolites. The study also probed for potential structural homology between the plant PAL enzyme and the human MYBPC3 protein, a sarcomeric constituent whose mutations are a predominant genetic etiology for familial hypertrophic cardiomyopathy. The methodological framework integrated a suite of bioinformatic applications. Protein sequence homology was assessed using BLASTp algorithms, while tertiary protein architecture was predicted via the Swiss-Model workspace. Molecular docking simulations, executed with AutoDock, characterized putative protein-ligand interfaces. Complementary analyses on dedicated computational servers facilitated active site prognostication, determination of pivotal residue constituents, and evaluations of conformational stability. Comparative sequence alignment established a lack of significant structural conservation between the PAL and MYBPC3 polypeptides. Notwithstanding this divergence, molecular docking simulations demonstrated a capacity for oligomeric procyanidin (OPC) ligands to engage the PAL active site, a interaction characterized by favorable binding affinities and the formation of stable hydrogen bonds. Furthermore, structural profiling elucidated functional domains and critical catalytic residues intrinsic to PAL function. In conclusion, this research underscores the integral role of the PAL gene in the OPC biosynthetic machinery of hawthorn, as delineated by sophisticated in silico methodologies. The absence of structural mimicry with MYBPC3 confirms the functional specificity of each protein within their respective biological contexts. These insights provide a foundational platform for subsequent exploration in metabolic engineering and the development of plant-based therapeutic agents.

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