FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3160993960> ?p ?o ?g. }

• W3160993960 endingPage "1039" @default.
• W3160993960 startingPage "1030" @default.
• W3160993960 abstract "A common strategy employed in antibacterial drug discovery is the targeting of biosynthetic processes that are essential and specific for the pathogen. Specificity in particular avoids undesirable interactions with potential enzymatic counterparts in the human host, and it ensures on-target toxicity. Synthesis of pantothenate (Vitamine B5), which is a precursor of the acyl carrier coenzyme A, is an example of such a pathway. In Mycobacterium tuberculosis (Mtb), which is the causative agent of tuberculosis (TB), pantothenate is formed by pantothenate synthase, utilizing D-pantoate and β-Ala as substrates. β-Ala is mainly formed by the decarboxylation of l-aspartate, generated by the decarboxylase PanD, which is a homo-oliogomer in solution. Pyrazinoic acid (POA), which is the bioactive form of the TB prodrug pyrazinamide, binds and inhibits PanD activity weakly. Here, we generated a library of recombinant Mtb PanD mutants based on structural information and PZA/POA resistance mutants. Alterations in oligomer formation, enzyme activity, and/or POA binding were observed in respective mutants, providing insights into essential amino acids for Mtb PanD’s proper structural assembly, decarboxylation activity and drug interaction. This information provided the platform for the design of novel POA analogues with modifications at position 3 of the pyrazine ring. Analogue 2, which incorporates a bulky naphthamido group at this position, displayed a 1000-fold increase in enzyme inhibition, compared to POA, along with moderately improved antimycobacterial activity. The data demonstrate that an improved understanding of mechanistic and enzymatic features of key metabolic enzymes can stimulate design of more-potent PanD inhibitors." @default.
• W3160993960 created "2021-05-24" @default.
• W3160993960 creator A5000319999 @default.
• W3160993960 creator A5000761449 @default.
• W3160993960 creator A5001805819 @default.
• W3160993960 creator A5014419330 @default.
• W3160993960 creator A5025043446 @default.
• W3160993960 creator A5063384719 @default.
• W3160993960 creator A5067367555 @default.
• W3160993960 creator A5068752989 @default.
• W3160993960 creator A5073666536 @default.
• W3160993960 creator A5076709370 @default.
• W3160993960 creator A5090609840 @default.
• W3160993960 date "2021-05-13" @default.
• W3160993960 modified "2023-09-25" @default.
• W3160993960 title "<i>Mycobacterium tuberculosis</i> PanD Structure–Function Analysis and Identification of a Potent Pyrazinoic Acid-Derived Enzyme Inhibitor" @default.
• W3160993960 cites W1889103490 @default.
• W3160993960 cites W1907908820 @default.
• W3160993960 cites W2016385268 @default.
• W3160993960 cites W2019536074 @default.
• W3160993960 cites W2036218860 @default.
• W3160993960 cites W2046352089 @default.
• W3160993960 cites W2062383296 @default.
• W3160993960 cites W2065130119 @default.
• W3160993960 cites W2075505441 @default.
• W3160993960 cites W2080231076 @default.
• W3160993960 cites W2083155903 @default.
• W3160993960 cites W2111400483 @default.
• W3160993960 cites W2150740864 @default.
• W3160993960 cites W2167190401 @default.
• W3160993960 cites W2167551601 @default.
• W3160993960 cites W2188306988 @default.
• W3160993960 cites W2310217259 @default.
• W3160993960 cites W2466404575 @default.
• W3160993960 cites W2594259713 @default.
• W3160993960 cites W2763376787 @default.
• W3160993960 cites W2984041411 @default.
• W3160993960 cites W2999416445 @default.
• W3160993960 cites W3000998482 @default.
• W3160993960 cites W3010633141 @default.
• W3160993960 cites W3014691287 @default.
• W3160993960 cites W3092885106 @default.
• W3160993960 doi "https://doi.org/10.1021/acschembio.1c00131" @default.
• W3160993960 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8217388" @default.
• W3160993960 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33984234" @default.
• W3160993960 hasPublicationYear "2021" @default.
• W3160993960 type Work @default.
• W3160993960 sameAs 3160993960 @default.
• W3160993960 citedByCount "8" @default.
• W3160993960 countsByYear W31609939602022 @default.
• W3160993960 countsByYear W31609939602023 @default.
• W3160993960 crossrefType "journal-article" @default.
• W3160993960 hasAuthorship W3160993960A5000319999 @default.
• W3160993960 hasAuthorship W3160993960A5000761449 @default.
• W3160993960 hasAuthorship W3160993960A5001805819 @default.
• W3160993960 hasAuthorship W3160993960A5014419330 @default.
• W3160993960 hasAuthorship W3160993960A5025043446 @default.
• W3160993960 hasAuthorship W3160993960A5063384719 @default.
• W3160993960 hasAuthorship W3160993960A5067367555 @default.
• W3160993960 hasAuthorship W3160993960A5068752989 @default.
• W3160993960 hasAuthorship W3160993960A5073666536 @default.
• W3160993960 hasAuthorship W3160993960A5076709370 @default.
• W3160993960 hasAuthorship W3160993960A5090609840 @default.
• W3160993960 hasBestOaLocation W31609939602 @default.
• W3160993960 hasConcept C104317684 @default.
• W3160993960 hasConcept C108215921 @default.
• W3160993960 hasConcept C142724271 @default.
• W3160993960 hasConcept C143065580 @default.
• W3160993960 hasConcept C181199279 @default.
• W3160993960 hasConcept C185592680 @default.
• W3160993960 hasConcept C2777272437 @default.
• W3160993960 hasConcept C2777975735 @default.
• W3160993960 hasConcept C2781069245 @default.
• W3160993960 hasConcept C523546767 @default.
• W3160993960 hasConcept C54355233 @default.
• W3160993960 hasConcept C55493867 @default.
• W3160993960 hasConcept C71924100 @default.
• W3160993960 hasConcept C74187038 @default.
• W3160993960 hasConcept C86803240 @default.
• W3160993960 hasConceptScore W3160993960C104317684 @default.
• W3160993960 hasConceptScore W3160993960C108215921 @default.
• W3160993960 hasConceptScore W3160993960C142724271 @default.
• W3160993960 hasConceptScore W3160993960C143065580 @default.
• W3160993960 hasConceptScore W3160993960C181199279 @default.
• W3160993960 hasConceptScore W3160993960C185592680 @default.
• W3160993960 hasConceptScore W3160993960C2777272437 @default.
• W3160993960 hasConceptScore W3160993960C2777975735 @default.
• W3160993960 hasConceptScore W3160993960C2781069245 @default.
• W3160993960 hasConceptScore W3160993960C523546767 @default.
• W3160993960 hasConceptScore W3160993960C54355233 @default.
• W3160993960 hasConceptScore W3160993960C55493867 @default.
• W3160993960 hasConceptScore W3160993960C71924100 @default.
• W3160993960 hasConceptScore W3160993960C74187038 @default.
• W3160993960 hasConceptScore W3160993960C86803240 @default.
• W3160993960 hasFunder F4320320709 @default.
• W3160993960 hasFunder F4320337355 @default.
• W3160993960 hasIssue "6" @default.
• W3160993960 hasLocation W31609939601 @default.

• next