FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385655661> ?p ?o ?g. }

• W4385655661 endingPage "2596" @default.
• W4385655661 startingPage "2587" @default.
• W4385655661 abstract "Because purine nucleotides are essential for all life, differences between how microbes and humans metabolize purines can be exploited for the development of antimicrobial therapies. While humans biosynthesize purine nucleotides in a 10-step pathway, most microbes utilize an additional 11th enzymatic activity. The human enzyme, aminoimidazole ribonucleotide (AIR) carboxylase generates the product 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) directly. Most microbes, however, require two separate enzymes, a synthetase (PurK) and a mutase (PurE), and proceed through the intermediate, N5-CAIR. Toward the development of therapeutics that target these differences, we have solved crystal structures of the N5-CAIR mutase of the human pathogens Legionella pneumophila (LpPurE) and Burkholderia cenocepacia (BcPurE) and used a structure-guided approach to identify inhibitors. Analysis of the structures reveals a highly conserved fold and active site architecture. Using this data, and three additional structures of PurE enzymes, we screened a library of FDA-approved compounds in silico and identified a set of 25 candidates for further analysis. Among these, we identified several new PurE inhibitors with micromolar IC50 values. Several of these compounds, including the α1-blocker Alfuzosin, inhibit the microbial PurE enzymes much more effectively than the human homologue. These structures and the newly described PurE inhibitors are valuable tools to aid in further studies of this enzyme and provide a foundation for the development of compounds that target differences between human and microbial purine metabolism." @default.
• W4385655661 created "2023-08-09" @default.
• W4385655661 creator A5005484069 @default.
• W4385655661 creator A5006004732 @default.
• W4385655661 creator A5010024648 @default.
• W4385655661 creator A5015844740 @default.
• W4385655661 creator A5043469393 @default.
• W4385655661 creator A5072534812 @default.
• W4385655661 creator A5076092420 @default.
• W4385655661 creator A5089725528 @default.
• W4385655661 date "2023-08-08" @default.
• W4385655661 modified "2023-10-14" @default.
• W4385655661 title "Structure-Guided Discovery of N⁵-CAIR Mutase Inhibitors" @default.
• W4385655661 cites W1800471089 @default.
• W4385655661 cites W1902292659 @default.
• W4385655661 cites W1969430061 @default.
• W4385655661 cites W1972949624 @default.
• W4385655661 cites W1980309708 @default.
• W4385655661 cites W1982353844 @default.
• W4385655661 cites W1984039745 @default.
• W4385655661 cites W1988100608 @default.
• W4385655661 cites W1992531977 @default.
• W4385655661 cites W2007857508 @default.
• W4385655661 cites W2009545612 @default.
• W4385655661 cites W2016956375 @default.
• W4385655661 cites W2024074032 @default.
• W4385655661 cites W2027482274 @default.
• W4385655661 cites W2028547310 @default.
• W4385655661 cites W2035503835 @default.
• W4385655661 cites W2038840577 @default.
• W4385655661 cites W2042572511 @default.
• W4385655661 cites W2054620060 @default.
• W4385655661 cites W2056040703 @default.
• W4385655661 cites W2059832194 @default.
• W4385655661 cites W2065362994 @default.
• W4385655661 cites W2082846873 @default.
• W4385655661 cites W2094476648 @default.
• W4385655661 cites W2100678718 @default.
• W4385655661 cites W2105288217 @default.
• W4385655661 cites W2106246537 @default.
• W4385655661 cites W2106798080 @default.
• W4385655661 cites W2107417369 @default.
• W4385655661 cites W2112688493 @default.
• W4385655661 cites W2123859101 @default.
• W4385655661 cites W2126687190 @default.
• W4385655661 cites W2131719921 @default.
• W4385655661 cites W2135748133 @default.
• W4385655661 cites W2144081223 @default.
• W4385655661 cites W2147458973 @default.
• W4385655661 cites W2155188941 @default.
• W4385655661 cites W2157517801 @default.
• W4385655661 cites W2160695434 @default.
• W4385655661 cites W2214049718 @default.
• W4385655661 cites W2321713662 @default.
• W4385655661 cites W2404280981 @default.
• W4385655661 cites W2558795906 @default.
• W4385655661 cites W2905424382 @default.
• W4385655661 cites W2935971413 @default.
• W4385655661 cites W3083406432 @default.
• W4385655661 cites W4248872320 @default.
• W4385655661 cites W4282922306 @default.
• W4385655661 doi "https://doi.org/10.1021/acs.biochem.2c00705" @default.
• W4385655661 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37552766" @default.
• W4385655661 hasPublicationYear "2023" @default.
• W4385655661 type Work @default.
• W4385655661 citedByCount "0" @default.
• W4385655661 crossrefType "journal-article" @default.
• W4385655661 hasAuthorship W4385655661A5005484069 @default.
• W4385655661 hasAuthorship W4385655661A5006004732 @default.
• W4385655661 hasAuthorship W4385655661A5010024648 @default.
• W4385655661 hasAuthorship W4385655661A5015844740 @default.
• W4385655661 hasAuthorship W4385655661A5043469393 @default.
• W4385655661 hasAuthorship W4385655661A5072534812 @default.
• W4385655661 hasAuthorship W4385655661A5076092420 @default.
• W4385655661 hasAuthorship W4385655661A5089725528 @default.
• W4385655661 hasConcept C104317684 @default.
• W4385655661 hasConcept C169586020 @default.
• W4385655661 hasConcept C181199279 @default.
• W4385655661 hasConcept C185592680 @default.
• W4385655661 hasConcept C2775905019 @default.
• W4385655661 hasConcept C2776476023 @default.
• W4385655661 hasConcept C2777552656 @default.
• W4385655661 hasConcept C41183919 @default.
• W4385655661 hasConcept C512185932 @default.
• W4385655661 hasConcept C55493867 @default.
• W4385655661 hasConcept C86803240 @default.
• W4385655661 hasConcept C98892162 @default.
• W4385655661 hasConceptScore W4385655661C104317684 @default.
• W4385655661 hasConceptScore W4385655661C169586020 @default.
• W4385655661 hasConceptScore W4385655661C181199279 @default.
• W4385655661 hasConceptScore W4385655661C185592680 @default.
• W4385655661 hasConceptScore W4385655661C2775905019 @default.
• W4385655661 hasConceptScore W4385655661C2776476023 @default.
• W4385655661 hasConceptScore W4385655661C2777552656 @default.
• W4385655661 hasConceptScore W4385655661C41183919 @default.
• W4385655661 hasConceptScore W4385655661C512185932 @default.
• W4385655661 hasConceptScore W4385655661C55493867 @default.
• W4385655661 hasConceptScore W4385655661C86803240 @default.

• next