FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1484451878> ?p ?o ?g. }

• W1484451878 endingPage "999" @default.
• W1484451878 startingPage "991" @default.
• W1484451878 abstract "The proposed mechanistic pathway for the reaction catalyzed by 3-deoxy-D-manno-2-octulosonate-8-phosphate (Kdo8P) synthase was examined in terms of the structure of the putative bisphosphate intermediate. Two 2-deoxy analogues of the product Kdo8P, having been structurally prohibited from undergoing the ring-opening and possessing the stereochemistry of either the alpha-pyranase (compound 1) or the beta-pyranose form (compound 2) of the product, were synthesized and probed as inhibitors for the synthase. It was found that both analogues bind to the enzyme and are competitive inhibitors with respect to phosphoenolpyruvate binding, having Ki values of 470 microM and 303 microM, respectively. Comparison of this data to the Ki value of the tautomeric mixture of the product Kdo8P (Ki = 590 microM) suggests that both the alpha- and the beta-pyranose anomers (65.8% and 3.1%, respectively at neutral pH) bind to the enzyme with a slight (1.13 kJ/mol) preference for the beta-anomer, and that the C2 hydroxyl does not contribute to the binding. This uncertain stereochemical preference exhibited by the enzyme for the stereoisomers at the anomeric carbon suggests that the carboxylate binding site of the product is indistinct, while the hydroxyl and carboxylate binding sites may be interchangeable. More importantly, however, the isosteric phosphonate analogue 2,6-anhydro-3-deoxy-2 beta-phosphonylmethyl-8-phosphate-D-glycero-D-talo-octonate (3), which mimics the topological and electrostatic properties of the proposed cyclic intermediate, was found to be the most potent inhibitor of the enzyme with a Ki value of 5 microM. Two hitherto unrecognized aspects of the mechanism of the synthase were identified. First, the results showing that the cyclic analogues 1, 2 and 3 are inhibitors of the enzyme whereas the previously reported acyclic analogue, which contains no carbonyl group at C2 and may thus resemble the open-chain form of Kdo8P, is not an inhibitor, suggest that the pyranose form and not the open-chain acyclic form of the putative bisphosphate intermediate is handled by the enzyme. Second, since the overall stereochemical course of the transformation mediated by the synthase has been shown to involve si face addition of phosphoenolpyruvate to the re face of the carbonyl of arabinose 5-phosphate, the present observation involving analogue 3 suggest that the bisphosphate intermediate formed during the initial steps of synthesis may have the pyranose structure with the anomeric phosphate located in the beta-configuration." @default.
• W1484451878 created "2016-06-24" @default.
• W1484451878 creator A5006681574 @default.
• W1484451878 creator A5042711695 @default.
• W1484451878 creator A5046126284 @default.
• W1484451878 creator A5053865350 @default.
• W1484451878 creator A5072258232 @default.
• W1484451878 date "1993-11-01" @default.
• W1484451878 modified "2023-10-04" @default.
• W1484451878 title "Catalytic mechanism of 3-deoxy-d-manno-2-octulosonate-8-phosphate synthase. The use of synthetic analogues to probe the structure of the putative reaction intermediate" @default.
• W1484451878 cites W1513277720 @default.
• W1484451878 cites W1519285535 @default.
• W1484451878 cites W1527171874 @default.
• W1484451878 cites W1535195547 @default.
• W1484451878 cites W1540339516 @default.
• W1484451878 cites W1555642282 @default.
• W1484451878 cites W1593852866 @default.
• W1484451878 cites W1601791150 @default.
• W1484451878 cites W1606816308 @default.
• W1484451878 cites W1912410317 @default.
• W1484451878 cites W1947508812 @default.
• W1484451878 cites W1981335560 @default.
• W1484451878 cites W1988132884 @default.
• W1484451878 cites W1989785390 @default.
• W1484451878 cites W2001681283 @default.
• W1484451878 cites W2002712854 @default.
• W1484451878 cites W2004533078 @default.
• W1484451878 cites W2013758658 @default.
• W1484451878 cites W2021483591 @default.
• W1484451878 cites W2022035094 @default.
• W1484451878 cites W2024069406 @default.
• W1484451878 cites W2026360922 @default.
• W1484451878 cites W2033154191 @default.
• W1484451878 cites W2035429492 @default.
• W1484451878 cites W2049727156 @default.
• W1484451878 cites W2049839234 @default.
• W1484451878 cites W2062666691 @default.
• W1484451878 cites W2066490611 @default.
• W1484451878 cites W2077542581 @default.
• W1484451878 cites W2091185461 @default.
• W1484451878 cites W2115076556 @default.
• W1484451878 cites W2328010077 @default.
• W1484451878 cites W2949174101 @default.
• W1484451878 cites W4240282810 @default.
• W1484451878 cites W646419260 @default.
• W1484451878 doi "https://doi.org/10.1111/j.1432-1033.1993.tb18330.x" @default.
• W1484451878 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8223657" @default.
• W1484451878 hasPublicationYear "1993" @default.
• W1484451878 type Work @default.
• W1484451878 sameAs 1484451878 @default.
• W1484451878 citedByCount "47" @default.
• W1484451878 countsByYear W14844518782012 @default.
• W1484451878 countsByYear W14844518782014 @default.
• W1484451878 countsByYear W14844518782019 @default.
• W1484451878 crossrefType "journal-article" @default.
• W1484451878 hasAuthorship W1484451878A5006681574 @default.
• W1484451878 hasAuthorship W1484451878A5042711695 @default.
• W1484451878 hasAuthorship W1484451878A5046126284 @default.
• W1484451878 hasAuthorship W1484451878A5053865350 @default.
• W1484451878 hasAuthorship W1484451878A5072258232 @default.
• W1484451878 hasConcept C111233374 @default.
• W1484451878 hasConcept C112243037 @default.
• W1484451878 hasConcept C150757390 @default.
• W1484451878 hasConcept C181199279 @default.
• W1484451878 hasConcept C185592680 @default.
• W1484451878 hasConcept C2777626080 @default.
• W1484451878 hasConcept C2778074193 @default.
• W1484451878 hasConcept C2780434155 @default.
• W1484451878 hasConcept C34490408 @default.
• W1484451878 hasConcept C41183919 @default.
• W1484451878 hasConcept C55493867 @default.
• W1484451878 hasConcept C71240020 @default.
• W1484451878 hasConcept C7947691 @default.
• W1484451878 hasConceptScore W1484451878C111233374 @default.
• W1484451878 hasConceptScore W1484451878C112243037 @default.
• W1484451878 hasConceptScore W1484451878C150757390 @default.
• W1484451878 hasConceptScore W1484451878C181199279 @default.
• W1484451878 hasConceptScore W1484451878C185592680 @default.
• W1484451878 hasConceptScore W1484451878C2777626080 @default.
• W1484451878 hasConceptScore W1484451878C2778074193 @default.
• W1484451878 hasConceptScore W1484451878C2780434155 @default.
• W1484451878 hasConceptScore W1484451878C34490408 @default.
• W1484451878 hasConceptScore W1484451878C41183919 @default.
• W1484451878 hasConceptScore W1484451878C55493867 @default.
• W1484451878 hasConceptScore W1484451878C71240020 @default.
• W1484451878 hasConceptScore W1484451878C7947691 @default.
• W1484451878 hasIssue "3" @default.
• W1484451878 hasLocation W14844518781 @default.
• W1484451878 hasLocation W14844518782 @default.
• W1484451878 hasOpenAccess W1484451878 @default.
• W1484451878 hasPrimaryLocation W14844518781 @default.
• W1484451878 hasRelatedWork W1484451878 @default.
• W1484451878 hasRelatedWork W1966707588 @default.
• W1484451878 hasRelatedWork W1967369953 @default.
• W1484451878 hasRelatedWork W1981652652 @default.
• W1484451878 hasRelatedWork W2010090914 @default.
• W1484451878 hasRelatedWork W2018062847 @default.
• W1484451878 hasRelatedWork W2081063168 @default.

• next