FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2327846645> ?p ?o ?g. }

• W2327846645 endingPage "2384" @default.
• W2327846645 startingPage "2372" @default.
• W2327846645 abstract "The central importance of chorismate enzymes in bacteria, fungi, parasites, and plants combined with their absence in mammals makes them attractive targets for antimicrobials and herbicides. Two of these enzymes, anthranilate synthase (AS) and aminodeoxychorismate synthase (ADCS), are structurally and mechanistically similar. The first catalytic step, amination at C2, is common between them, but AS additionally catalyzes pyruvate elimination, aromatizing the aminated intermediate to anthranilate. Despite prior attempts, the conversion of a pyruvate elimination-deficient enzyme into an elimination-proficient one has not been reported. Janus, a bioinformatics method for predicting mutations required to functionally interconvert homologous enzymes, was employed to predict mutations to convert ADCS into AS. A genetic selection on a library of Janus-predicted mutations was performed. Complementation of an AS-deficient strain of Escherichia coli grown on minimal medium led to several ADCS mutants that allow growth in 6 days compared to 2 days for wild-type AS. The purified mutant enzymes catalyze the conversion of chorismate to anthranilate at rates that are ∼50% of the rate of wild-type ADCS-catalyzed conversion of chorismate to aminodeoxychorismate. The residues mutated do not contact the substrate. Molecular dynamics studies suggest that pyruvate elimination is controlled by the conformation of the C2-aminated intermediate. Enzymes that catalyze elimination favor the equatorial conformation, which presents the C2-H to a conserved active site lysine (Lys424) for deprotonation and maximizes stereoelectronic activation. Acid/base catalysis of pyruvate elimination was confirmed in AS and salicylate synthase by showing incorporation of a solvent-derived proton into the pyruvate methyl group and by solvent kinetic isotope effects on pyruvate elimination catalyzed by AS." @default.
• W2327846645 created "2016-06-24" @default.
• W2327846645 creator A5016269410 @default.
• W2327846645 creator A5028944791 @default.
• W2327846645 creator A5070262517 @default.
• W2327846645 creator A5077684755 @default.
• W2327846645 creator A5078366579 @default.
• W2327846645 date "2015-04-02" @default.
• W2327846645 modified "2023-10-17" @default.
• W2327846645 title "Conversion of Aminodeoxychorismate Synthase into Anthranilate Synthase with Janus Mutations: Mechanism of Pyruvate Elimination Catalyzed by Chorismate Enzymes" @default.
• W2327846645 cites W1597265946 @default.
• W2327846645 cites W1967509688 @default.
• W2327846645 cites W1974071568 @default.
• W2327846645 cites W1983339139 @default.
• W2327846645 cites W1988837867 @default.
• W2327846645 cites W1990966227 @default.
• W2327846645 cites W2003288605 @default.
• W2327846645 cites W2013214522 @default.
• W2327846645 cites W2020047292 @default.
• W2327846645 cites W2024384471 @default.
• W2327846645 cites W2027185526 @default.
• W2327846645 cites W2028326590 @default.
• W2327846645 cites W2032427088 @default.
• W2327846645 cites W2043462009 @default.
• W2327846645 cites W2046878357 @default.
• W2327846645 cites W2050343641 @default.
• W2327846645 cites W2054018362 @default.
• W2327846645 cites W2054705875 @default.
• W2327846645 cites W2056153343 @default.
• W2327846645 cites W2064491541 @default.
• W2327846645 cites W2069302400 @default.
• W2327846645 cites W2070045719 @default.
• W2327846645 cites W2073518671 @default.
• W2327846645 cites W2081191597 @default.
• W2327846645 cites W2083799886 @default.
• W2327846645 cites W2088558902 @default.
• W2327846645 cites W2094076636 @default.
• W2327846645 cites W2099099776 @default.
• W2327846645 cites W2106814386 @default.
• W2327846645 cites W2106857639 @default.
• W2327846645 cites W2110585845 @default.
• W2327846645 cites W2127272780 @default.
• W2327846645 cites W2139044055 @default.
• W2327846645 cites W2142920796 @default.
• W2327846645 cites W2162959060 @default.
• W2327846645 cites W2344049794 @default.
• W2327846645 cites W241954630 @default.
• W2327846645 cites W2950851297 @default.
• W2327846645 doi "https://doi.org/10.1021/acs.biochem.5b00013" @default.
• W2327846645 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25710100" @default.
• W2327846645 hasPublicationYear "2015" @default.
• W2327846645 type Work @default.
• W2327846645 sameAs 2327846645 @default.
• W2327846645 citedByCount "14" @default.
• W2327846645 countsByYear W23278466452015 @default.
• W2327846645 countsByYear W23278466452016 @default.
• W2327846645 countsByYear W23278466452017 @default.
• W2327846645 countsByYear W23278466452018 @default.
• W2327846645 countsByYear W23278466452019 @default.
• W2327846645 countsByYear W23278466452021 @default.
• W2327846645 countsByYear W23278466452022 @default.
• W2327846645 crossrefType "journal-article" @default.
• W2327846645 hasAuthorship W2327846645A5016269410 @default.
• W2327846645 hasAuthorship W2327846645A5028944791 @default.
• W2327846645 hasAuthorship W2327846645A5070262517 @default.
• W2327846645 hasAuthorship W2327846645A5077684755 @default.
• W2327846645 hasAuthorship W2327846645A5078366579 @default.
• W2327846645 hasConcept C104317684 @default.
• W2327846645 hasConcept C112243037 @default.
• W2327846645 hasConcept C143065580 @default.
• W2327846645 hasConcept C181199279 @default.
• W2327846645 hasConcept C185592680 @default.
• W2327846645 hasConcept C55493867 @default.
• W2327846645 hasConcept C71240020 @default.
• W2327846645 hasConceptScore W2327846645C104317684 @default.
• W2327846645 hasConceptScore W2327846645C112243037 @default.
• W2327846645 hasConceptScore W2327846645C143065580 @default.
• W2327846645 hasConceptScore W2327846645C181199279 @default.
• W2327846645 hasConceptScore W2327846645C185592680 @default.
• W2327846645 hasConceptScore W2327846645C55493867 @default.
• W2327846645 hasConceptScore W2327846645C71240020 @default.
• W2327846645 hasIssue "14" @default.
• W2327846645 hasLocation W23278466451 @default.
• W2327846645 hasLocation W23278466452 @default.
• W2327846645 hasOpenAccess W2327846645 @default.
• W2327846645 hasPrimaryLocation W23278466451 @default.
• W2327846645 hasRelatedWork W1978556499 @default.
• W2327846645 hasRelatedWork W1984834769 @default.
• W2327846645 hasRelatedWork W2044028228 @default.
• W2327846645 hasRelatedWork W2047730886 @default.
• W2327846645 hasRelatedWork W2077224613 @default.
• W2327846645 hasRelatedWork W2094337488 @default.
• W2327846645 hasRelatedWork W2155835698 @default.
• W2327846645 hasRelatedWork W2350587855 @default.
• W2327846645 hasRelatedWork W2364134146 @default.
• W2327846645 hasRelatedWork W2994288809 @default.
• W2327846645 hasVolume "54" @default.
• W2327846645 isParatext "false" @default.

• next