FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2078107601> ?p ?o ?g. }

• W2078107601 endingPage "323" @default.
• W2078107601 startingPage "313" @default.
• W2078107601 abstract "The role of Try-81 in the reaction catalyzed by Saccharomyces cerevisiae sterol 24-C-methyltransferase (Erg6p) was investigated kinetically and for product differences against a panel of position-81 mutants in which Tyr was substituted with Trp, Phe, Ile, Leu, Val and Ala. The residue chosen for mutation is one that was reported previously to accept fecosterol and yield a set 24-ethyl (idene) sterol products typical of plants, showing the amino acid residue is located close to the transient C25 carbocation intermediate in the active site. One group of mutants (aromatic) tested with the natural substrate zymosterol accelerated the C-methylation reaction (kcat/Km) whereas the other group of mutants (aliphatics) decreased catalytic competence as the amino acid side chain was downsized. Mutating to aromatic and assaying with the substrate analog designed as a suicide substrate 26,27-dehydrozymosterol favored C26-monol formation, whereas mutating to the aliphatic of smaller size favored C26-diol formation (a measure of enzyme alkylation). In no case was zymosterol converted to an intermediate that formed a C25-diol. Thermodynamic analysis (determination of Ea, ΔG‡, ΔH‡ and TΔS‡) for the C-methylation reaction performed by these enzymes assayed with the substrate and its analog or zymosterol paired with the “charged’ high energy intermediate (HEI) analogs 24(R,S)25,epiminolanosterol and 25-azalanosterol or “neutral” membrane insert ergosterol showed that mutation to aromatics can reduce inhibitor potency (measured as Km/Ki), yet catalysis can improve in Trp81 by the introduction of a gain in free energy associated with stabilization of the transition state of a rate-controlling step directed toward turnover. Alternatively, mutation to the smaller aliphatic amino acid side chains led to a destabilization in the active site structure which was accompanied by increases in the partition ratios associated with abortive complex formation. The results are explained by consideration of the functional differences attributed to Tyr81 substitution to aromatics and aliphatics of different size involved with cation-π or hydrogen bonding interactions and in the activation barriers required of differing side chain conformations to orient the reactants in the direction of turnover versus enzyme inactivation." @default.
• W2078107601 created "2016-06-24" @default.
• W2078107601 creator A5002688503 @default.
• W2078107601 creator A5023277250 @default.
• W2078107601 creator A5064294448 @default.
• W2078107601 date "2008-09-01" @default.
• W2078107601 modified "2023-10-14" @default.
• W2078107601 title "Yeast sterol C24-methyltransferase: Role of highly conserved tyrosine-81 in catalytic competence studied by site-directed mutagenesis and thermodynamic analysis" @default.
• W2078107601 cites W1489046430 @default.
• W2078107601 cites W1532839418 @default.
• W2078107601 cites W1576525527 @default.
• W2078107601 cites W1967526695 @default.
• W2078107601 cites W1967711052 @default.
• W2078107601 cites W1969802703 @default.
• W2078107601 cites W1971805633 @default.
• W2078107601 cites W1975312126 @default.
• W2078107601 cites W1978856256 @default.
• W2078107601 cites W1983552699 @default.
• W2078107601 cites W1994224956 @default.
• W2078107601 cites W1995734836 @default.
• W2078107601 cites W2002470296 @default.
• W2078107601 cites W2003102783 @default.
• W2078107601 cites W2008517648 @default.
• W2078107601 cites W2013263481 @default.
• W2078107601 cites W2024156945 @default.
• W2078107601 cites W2032159769 @default.
• W2078107601 cites W2034673901 @default.
• W2078107601 cites W2037748577 @default.
• W2078107601 cites W2041642208 @default.
• W2078107601 cites W2047817142 @default.
• W2078107601 cites W2051257038 @default.
• W2078107601 cites W2058752820 @default.
• W2078107601 cites W2059398375 @default.
• W2078107601 cites W2064979599 @default.
• W2078107601 cites W2066659033 @default.
• W2078107601 cites W2068991842 @default.
• W2078107601 cites W2070216979 @default.
• W2078107601 cites W2070456262 @default.
• W2078107601 cites W2073700640 @default.
• W2078107601 cites W2073888758 @default.
• W2078107601 cites W2074629800 @default.
• W2078107601 cites W2076771365 @default.
• W2078107601 cites W2082969011 @default.
• W2078107601 cites W2085475030 @default.
• W2078107601 cites W2090025142 @default.
• W2078107601 cites W2106004163 @default.
• W2078107601 cites W2106216001 @default.
• W2078107601 cites W2106855080 @default.
• W2078107601 cites W2107266240 @default.
• W2078107601 cites W2121936687 @default.
• W2078107601 cites W2139455549 @default.
• W2078107601 cites W2140857432 @default.
• W2078107601 cites W2148735872 @default.
• W2078107601 cites W2161302855 @default.
• W2078107601 doi "https://doi.org/10.1016/j.abb.2008.05.016" @default.
• W2078107601 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18555004" @default.
• W2078107601 hasPublicationYear "2008" @default.
• W2078107601 type Work @default.
• W2078107601 sameAs 2078107601 @default.
• W2078107601 citedByCount "19" @default.
• W2078107601 countsByYear W20781076012013 @default.
• W2078107601 countsByYear W20781076012014 @default.
• W2078107601 countsByYear W20781076012015 @default.
• W2078107601 countsByYear W20781076012017 @default.
• W2078107601 countsByYear W20781076012018 @default.
• W2078107601 countsByYear W20781076012020 @default.
• W2078107601 countsByYear W20781076012022 @default.
• W2078107601 crossrefType "journal-article" @default.
• W2078107601 hasAuthorship W2078107601A5002688503 @default.
• W2078107601 hasAuthorship W2078107601A5023277250 @default.
• W2078107601 hasAuthorship W2078107601A5064294448 @default.
• W2078107601 hasConcept C104317684 @default.
• W2078107601 hasConcept C143065580 @default.
• W2078107601 hasConcept C161790260 @default.
• W2078107601 hasConcept C181199279 @default.
• W2078107601 hasConcept C185592680 @default.
• W2078107601 hasConcept C2777910421 @default.
• W2078107601 hasConcept C2777992278 @default.
• W2078107601 hasConcept C2778163477 @default.
• W2078107601 hasConcept C2778718757 @default.
• W2078107601 hasConcept C33288867 @default.
• W2078107601 hasConcept C41183919 @default.
• W2078107601 hasConcept C552990157 @default.
• W2078107601 hasConcept C55493867 @default.
• W2078107601 hasConcept C56856141 @default.
• W2078107601 hasConcept C71240020 @default.
• W2078107601 hasConcept C91965660 @default.
• W2078107601 hasConceptScore W2078107601C104317684 @default.
• W2078107601 hasConceptScore W2078107601C143065580 @default.
• W2078107601 hasConceptScore W2078107601C161790260 @default.
• W2078107601 hasConceptScore W2078107601C181199279 @default.
• W2078107601 hasConceptScore W2078107601C185592680 @default.
• W2078107601 hasConceptScore W2078107601C2777910421 @default.
• W2078107601 hasConceptScore W2078107601C2777992278 @default.
• W2078107601 hasConceptScore W2078107601C2778163477 @default.
• W2078107601 hasConceptScore W2078107601C2778718757 @default.
• W2078107601 hasConceptScore W2078107601C33288867 @default.
• W2078107601 hasConceptScore W2078107601C41183919 @default.

• next