Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum

Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A (PDB: 3LD6)....

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Published in:Marine drugs 2017-04, Vol.15 (4), p.107
Main Authors: Yuan, Yongze, Han, Rui, Cao, Qianwen, Yu, Jinhui, Mao, Jiali, Zhang, Tingfu, Wang, Shengqiang, Niu, Yuhui, Liu, Deli
Format: Article
Language:English
Subjects:
Antifungal Agents - metabolism
Biosynthesis
Crystal structure
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450
Cytochromes
demethylase inhibitors
Drug Design
Drug development
Drugs
Dynamics
Enzymes
Fungal Proteins - metabolism
Fungicides
Homology
Humans
Inhibitors
Lead compounds
Ligands
Modelling
molecular docking
Molecular Docking Simulation - methods
Molecular dynamics
Molecular Dynamics Simulation
Penicillium - metabolism
Penicillium italicum
pharmacophore
PiCYP51A
Quality control
Simulation
Sterols
virtual screening
Zinc
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cited_by cdi_FETCH-LOGICAL-c472t-f986b69dc880f0ecacff6ffc2fd69139b8987ad7dd79b617d62796daf36a75fe3
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creator Yuan, Yongze
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Niu, Yuhui
Liu, Deli
description Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A (PDB: 3LD6). Molecular dynamics (MD) simulation was operated to relax the initial model and followed by quality assessment using PROCHECK program. On the basis of the docking information on the currently available CYP51s with the patent demethylase inhibitors (DMIs), pharmacophore-based virtual screening combined with docking analysis was performed to pick out twelve new compounds from ZINC database. Six hits revealed in the ligand database suggested potential ability to inhibit PiCYP51A. Compared to patent fungicide triazolone, the top three lead compounds had similar or higher affinity with the target enzyme, and accordingly, exhibited comparable or lower EC values to isolates. The results could provide references for de novo antifungal drug design.
doi_str_mv 10.3390/md15040107
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source PubMed (Medline); Publicly Available Content Database
subjects Antifungal Agents - metabolism
Biosynthesis
Crystal structure
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450
Cytochromes
demethylase inhibitors
Drug Design
Drug development
Drugs
Dynamics
Enzymes
Fungal Proteins - metabolism
Fungicides
Homology
Humans
Inhibitors
Lead compounds
Ligands
Modelling
molecular docking
Molecular Docking Simulation - methods
Molecular dynamics
Molecular Dynamics Simulation
Penicillium - metabolism
Penicillium italicum
pharmacophore
PiCYP51A
Quality control
Simulation
Sterols
virtual screening
Zinc
title Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum
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