نوع مقاله : علمی پژوهشی
نویسندگان
گروه زیستشناسی سلولی و مولکولی، دانشکده علوم زیستی و بیوتکنولوژی، دانشگاه شهید بهشتی، تهران، ایران
چکیده
کلیدواژهها
موضوعات
عنوان مقاله [English]
نویسندگان [English]
Chalcone synthase is a key enzyme in the flavonoid biosynthesis pathway, catalyzing the first committed step in phenolic secondary metabolite formation. Rydingia persica, a native Lamiaceae species traditionally used in Iranian medicine, is rich in bioactive compounds; however, structural data on its chalcone synthase (RpCHS) remain limited. In this study, the three-dimensional structure of RpCHS was predicted by homology modeling using the SWISS-MODEL server, and the binding affinity of twelve natural compounds to its active site was evaluated. The model was built based on the crystal structure of Oryza sativa (PDB: 4YJY, Chain A) with 86.01% sequence identity. Validation with ERRAT (96.54%) and Verify3D (80.83%) confirmed model quality. The active site is mainly surrounded by hydrophobic residues Phe215, Leu214, Leu266, and the catalytic triad Cys164, His303, and Asn336. Selected ligands—including flavonols, chalcone derivatives, and terpenoid/phenolic compounds (some reported metabolites in Lamiaceae with potential feedback inhibition roles)—were optimized using Chem3D and docked with AutoDock Vina. p-Coumaroyl-CoA was docked as a positive control (ΔG = −6.8 kcal/mol). Results showed binding free energies ranging from −8.4 to −5.8 kcal/mol, with chalcone derivatives and flavonols (xanthoangelol at −8.4 kcal/mol and quercetin at −8.0 kcal/mol) exhibiting stronger affinities than terpenoids. Interaction analysis using BIOVIA Discovery Studio Visualizer and LigPlot+ revealed that complex stability was primarily driven by hydrogen bonds, π–π interactions, and hydrophobic contacts. These findings indicate the potential of chalcone derivatives and flavonols as natural inhibitors and modulators of RpCHS and provide a basis for enzyme inhibitor discovery and understanding its regulatory mechanisms.
کلیدواژهها [English]
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