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http://elar.urfu.ru/handle/10995/90224
Название: | Structure-based virtual screening of pseudomonas aeruginosa lpxa inhibitors using pharmacophore-based approach |
Авторы: | Bhaskar, B. V. Babu, T. M. C. Rammohan, A. Zheng, G. Y. Zyryanov, G. V. Gu, W. Зырянов, Г. В. |
Дата публикации: | 2020 |
Издатель: | MDPI AG |
Библиографическое описание: | 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. |
Аннотация: | 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. |
Ключевые слова: | 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://elar.urfu.ru/handle/10995/90224 |
Условия доступа: | info:eu-repo/semantics/openAccess cc-by |
Идентификатор SCOPUS: | 85079339466 |
Идентификатор WOS: | 000522138500010 |
Идентификатор PURE: | 12247979 |
ISSN: | 2218-273X |
DOI: | 10.3390/biom10020266 |
Сведения о поддержке: | 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. |
Располагается в коллекциях: | Научные публикации ученых УрФУ, проиндексированные в SCOPUS и WoS CC |
Файлы этого ресурса:
Файл | Описание | Размер | Формат | |
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10.3390-biom10020266.pdf | 8,66 MB | Adobe PDF | Просмотреть/Открыть |
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