FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4297143400> ?p ?o ?g. }

• W4297143400 endingPage "1507.e6" @default.
• W4297143400 startingPage "1494" @default.
• W4297143400 abstract "•The structure of fungal pantothenate kinase (PanK) was solved at 1.8 Å resolution •A high-throughput chemical screen identified pyrimidone triazols as PanK inhibitors •Structure-function analyses revealed essential residues for PanK catalysis •Fungal PanK are valid targets for antifungal drug development Fungal infections are the leading cause of mortality by eukaryotic pathogens, with an estimated 150 million severe life-threatening cases and 1.7 million deaths reported annually. The rapid emergence of multidrug-resistant fungal isolates highlights the urgent need for new drugs with new mechanisms of action. In fungi, pantothenate phosphorylation, catalyzed by PanK enzyme, is the first step in the utilization of pantothenic acid and coenzyme A biosynthesis. In all fungi sequenced so far, this enzyme is encoded by a single PanK gene. Here, we report the crystal structure of a fungal PanK alone as well as with high-affinity inhibitors from a single chemotype identified through a high-throughput chemical screen. Structural, biochemical, and functional analyses revealed mechanisms governing substrate and ligand binding, dimerization, and catalysis and helped identify new compounds that inhibit the growth of several Candida species. The data validate PanK as a promising target for antifungal drug development. Fungal infections are the leading cause of mortality by eukaryotic pathogens, with an estimated 150 million severe life-threatening cases and 1.7 million deaths reported annually. The rapid emergence of multidrug-resistant fungal isolates highlights the urgent need for new drugs with new mechanisms of action. In fungi, pantothenate phosphorylation, catalyzed by PanK enzyme, is the first step in the utilization of pantothenic acid and coenzyme A biosynthesis. In all fungi sequenced so far, this enzyme is encoded by a single PanK gene. Here, we report the crystal structure of a fungal PanK alone as well as with high-affinity inhibitors from a single chemotype identified through a high-throughput chemical screen. Structural, biochemical, and functional analyses revealed mechanisms governing substrate and ligand binding, dimerization, and catalysis and helped identify new compounds that inhibit the growth of several Candida species. The data validate PanK as a promising target for antifungal drug development." @default.
• W4297143400 created "2022-09-27" @default.
• W4297143400 creator A5006007128 @default.
• W4297143400 creator A5007222260 @default.
• W4297143400 creator A5008481640 @default.
• W4297143400 creator A5009167189 @default.
• W4297143400 creator A5009309168 @default.
• W4297143400 creator A5020114753 @default.
• W4297143400 creator A5025341164 @default.
• W4297143400 creator A5039181160 @default.
• W4297143400 creator A5039902697 @default.
• W4297143400 creator A5041038683 @default.
• W4297143400 creator A5049605110 @default.
• W4297143400 creator A5050825309 @default.
• W4297143400 creator A5051588174 @default.
• W4297143400 creator A5053003138 @default.
• W4297143400 creator A5058081998 @default.
• W4297143400 creator A5060438205 @default.
• W4297143400 creator A5064672515 @default.
• W4297143400 creator A5068391532 @default.
• W4297143400 creator A5073329910 @default.
• W4297143400 date "2022-11-01" @default.
• W4297143400 modified "2023-10-03" @default.
• W4297143400 title "High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development" @default.
• W4297143400 cites W1524992328 @default.
• W4297143400 cites W1994957997 @default.
• W4297143400 cites W1997751445 @default.
• W4297143400 cites W2001573278 @default.
• W4297143400 cites W2021623802 @default.
• W4297143400 cites W2035503835 @default.
• W4297143400 cites W2054258577 @default.
• W4297143400 cites W2060809301 @default.
• W4297143400 cites W2123110434 @default.
• W4297143400 cites W2128311540 @default.
• W4297143400 cites W2134967712 @default.
• W4297143400 cites W2144081223 @default.
• W4297143400 cites W2163052215 @default.
• W4297143400 cites W2163341755 @default.
• W4297143400 cites W2180229411 @default.
• W4297143400 cites W2331253694 @default.
• W4297143400 cites W2376573086 @default.
• W4297143400 cites W2515371895 @default.
• W4297143400 cites W2766337129 @default.
• W4297143400 cites W2770016143 @default.
• W4297143400 cites W2770515423 @default.
• W4297143400 cites W2897325190 @default.
• W4297143400 cites W2967205921 @default.
• W4297143400 cites W2980681798 @default.
• W4297143400 cites W3006793634 @default.
• W4297143400 cites W3032047811 @default.
• W4297143400 cites W3116674544 @default.
• W4297143400 cites W3198464809 @default.
• W4297143400 cites W4210675630 @default.
• W4297143400 cites W4248872320 @default.
• W4297143400 doi "https://doi.org/10.1016/j.str.2022.09.001" @default.
• W4297143400 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36167065" @default.
• W4297143400 hasPublicationYear "2022" @default.
• W4297143400 type Work @default.
• W4297143400 citedByCount "3" @default.
• W4297143400 countsByYear W42971434002022 @default.
• W4297143400 countsByYear W42971434002023 @default.
• W4297143400 crossrefType "journal-article" @default.
• W4297143400 hasAuthorship W4297143400A5006007128 @default.
• W4297143400 hasAuthorship W4297143400A5007222260 @default.
• W4297143400 hasAuthorship W4297143400A5008481640 @default.
• W4297143400 hasAuthorship W4297143400A5009167189 @default.
• W4297143400 hasAuthorship W4297143400A5009309168 @default.
• W4297143400 hasAuthorship W4297143400A5020114753 @default.
• W4297143400 hasAuthorship W4297143400A5025341164 @default.
• W4297143400 hasAuthorship W4297143400A5039181160 @default.
• W4297143400 hasAuthorship W4297143400A5039902697 @default.
• W4297143400 hasAuthorship W4297143400A5041038683 @default.
• W4297143400 hasAuthorship W4297143400A5049605110 @default.
• W4297143400 hasAuthorship W4297143400A5050825309 @default.
• W4297143400 hasAuthorship W4297143400A5051588174 @default.
• W4297143400 hasAuthorship W4297143400A5053003138 @default.
• W4297143400 hasAuthorship W4297143400A5058081998 @default.
• W4297143400 hasAuthorship W4297143400A5060438205 @default.
• W4297143400 hasAuthorship W4297143400A5064672515 @default.
• W4297143400 hasAuthorship W4297143400A5068391532 @default.
• W4297143400 hasAuthorship W4297143400A5073329910 @default.
• W4297143400 hasBestOaLocation W42971434002 @default.
• W4297143400 hasConcept C134651460 @default.
• W4297143400 hasConcept C181199279 @default.
• W4297143400 hasConcept C2779123261 @default.
• W4297143400 hasConcept C2779548794 @default.
• W4297143400 hasConcept C2991737395 @default.
• W4297143400 hasConcept C55493867 @default.
• W4297143400 hasConcept C74187038 @default.
• W4297143400 hasConcept C86803240 @default.
• W4297143400 hasConcept C89423630 @default.
• W4297143400 hasConceptScore W4297143400C134651460 @default.
• W4297143400 hasConceptScore W4297143400C181199279 @default.
• W4297143400 hasConceptScore W4297143400C2779123261 @default.
• W4297143400 hasConceptScore W4297143400C2779548794 @default.
• W4297143400 hasConceptScore W4297143400C2991737395 @default.
• W4297143400 hasConceptScore W4297143400C55493867 @default.
• W4297143400 hasConceptScore W4297143400C74187038 @default.

• next