Please use this identifier to cite or link to this item:
|Title:||Structure-based virtual screening of pseudomonas aeruginosa lpxa inhibitors using pharmacophore-based approach|
|Authors:||Bhaskar, B. V.|
Babu, T. M. C.
Zheng, G. Y.
Zyryanov, G. V.
Зырянов, Г. В.
|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.|
ACYLTRANSFERASE PALPXA INHIBITOR
DRUG PROTEIN BINDING
|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|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.