Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/90224
Title: Structure-based virtual screening of pseudomonas aeruginosa lpxa inhibitors using pharmacophore-based approach
Authors: Bhaskar, B. V.
Babu, T. M. C.
Rammohan, A.
Zheng, G. Y.
Zyryanov, G. V.
Gu, W.
Зырянов, Г. В.
Issue Date: 2020
Publisher: MDPI AG
Citation: Structure-based virtual screening of pseudomonas aeruginosa lpxa inhibitors using pharmacophore-based approach / B. V. Bhaskar, T. M. C. Babu, A. Rammohan, G. Y. Zheng, et al. . — DOI 10.3390/biom10020266 // Biomolecules. — 2020. — Vol. 2. — Iss. 10. — 266.
Abstract: Multidrug resistance in Pseudomonas aeruginosa is a noticeable and ongoing major obstacle for inhibitor design. In P. aeruginosa, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) acetyltransferase (PaLpxA) is an essential enzyme of lipid A biosynthesis and an attractive drug target. PaLpxA is a homotrimer, and the binding pocket for its substrate, UDP-GlcNAc, is positioned between the monomer A–monomer B interface. The uracil moiety binds at one monomer A, the GlcNAc moiety binds at another monomer B, and a diphosphate form bonds with both monomers. The catalytic residues are conserved and display a similar catalytic mechanism across orthologs, but some distinctions exist between pocket sizes, residue differences, substrate positioning and specificity. The analysis of diversified pockets, volumes, and ligand positions was determined between orthologues that could aid in selective inhibitor development. Thenceforth, a complex-based pharmacophore model was generated and subjected to virtual screening to identify compounds with similar pharmacophoric properties. Docking and general Born-volume integral (GBVI) studies demonstrated 10 best lead compounds with selective inhibition properties with essential residues in the pocket. For biological access, these scaffolds complied with the Lipinski rule, no toxicity and drug likeness properties, and were considered as lead compounds. Hence, these scaffolds could be helpful for the development of potential selective PaLpxA inhibitors. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: ADME
DOCKING
GBVI
PALPXA
PHARMACOPHORE
VIRTUAL SCREENING
ACYLTRANSFERASE
ACYLTRANSFERASE PALPXA
ACYLTRANSFERASE PALPXA INHIBITOR
COMPOUND 162530
COMPOUND 293892
COMPOUND 321495
COMPOUND 353465
COMPOUND 366068
COMPOUND 3725291
COMPOUND 381868
COMPOUND 68858
COMPOUND 7529
COMPOUND 75326
ENZYME INHIBITOR
UNCLASSIFIED DRUG
ARTICLE
BINDING AFFINITY
DRUG ABSORPTION
DRUG BIOAVAILABILITY
DRUG DISTRIBUTION
DRUG EXCRETION
DRUG METABOLISM
DRUG PROTEIN BINDING
DRUG SCREENING
DRUG STRUCTURE
ENZYME INHIBITION
ENZYME STRUCTURE
MOLECULAR DOCKING
PHARMACOPHORE
PSEUDOMONAS AERUGINOSA
STRUCTURE ANALYSIS
TOXICITY TESTING
VIRTUAL REALITY
URI: http://hdl.handle.net/10995/90224
https://elar.urfu.ru/handle/10995/90224
Access: info:eu-repo/semantics/openAccess
cc-by
SCOPUS ID: 85079339466
WOS ID: 000522138500010
PURE ID: 12247979
ISSN: 2218-273X
DOI: 10.3390/biom10020266
metadata.dc.description.sponsorship: National Natural Science Foundation of China, NSFC: 31171209, 31071152
Funding: This research was funded by the National Natural Science Foundation of China (grant numbers: 31071152 and 31171209) to WG.
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

Files in This Item:
File Description SizeFormat 
10.3390-biom10020266.pdf8,66 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.