Matches in SemOpenAlex for { <https://semopenalex.org/work/W2085143209> ?p ?o ?g. }
Showing items 1 to 87 of
87
with 100 items per page.
- W2085143209 endingPage "16310" @default.
- W2085143209 startingPage "16301" @default.
- W2085143209 abstract "The beta-ketoacyl-acyl carrier protein synthase (KS) domain of the modular 6-deoxyerythronolide B synthase (DEBS) catalyzes the fundamental chain building reaction of polyketide biosynthesis. The KS-catalyzed reaction involves two discrete steps consisting of formation of an acyl-enzyme intermediate generated from the incoming acylthioester substrate and an active site cysteine residue, and the conversion of this intermediate to the beta-ketoacyl-acyl carrier protein product by a decarboxylative condensation with a paired methylmalonyl-SACP. We have determined the rate constants for the individual biochemical steps by a combination of protein acylation and transthioesterification experiments. The first-order rate constant (k(2)) for formation of the acyl-enzyme intermediate from [1-(14)C]-(2S,3R)-2-methyl-3-hydroxypentanoyl-SNAC (2) and recombinant DEBS module 2 is 5.8 +/- 2.6 min(-)(1), with a dissociation constant (K(S)) of 3.5 +/- 2.8 mM. The acyl-enzyme adduct was formed at a near-stoichiometric ratio of approximately 0.8:1. Transthioesterification between unlabeled diketide-SNAC 2 and N-[1-(14)C-acetyl]cysteamine gave a k(exch) of 0.15 +/- 0.06 min(-)(1), with a K(m) for HSNAC of 5.7 +/- 4.9 mM and a K(m) for 2 of 5.3 +/- 0.9 mM. Under the conditions that were used, k(exch) was equal to k(-)(2), the first-order rate constant for reversal of the acyl-enzyme-forming reaction. Since the rate of the decarboxylative condensation is much greater that the rate of reversion to the starting material (k(3) >> k(-)(2)), formation of the acyl-enzyme adduct is effectively irreversible, thereby establishing that the observed value of the specificity constant (k(cat)/K(m)) is solely a reflection of the intrinsic substrate specificity of the KS-catalyzed acyl-enzyme-forming reaction. These findings were also extended to a panel of diketide- and triketide-SNAC analogues, revealing that some substrate analogues that are not converted to product by DEBS module 2 form dead-end acyl-enzyme intermediates." @default.
- W2085143209 created "2016-06-24" @default.
- W2085143209 creator A5038399044 @default.
- W2085143209 creator A5060904695 @default.
- W2085143209 creator A5081975997 @default.
- W2085143209 creator A5089983022 @default.
- W2085143209 date "2004-11-25" @default.
- W2085143209 modified "2023-09-27" @default.
- W2085143209 title "Biochemical Analysis of the Substrate Specificity of the β-Ketoacyl-Acyl Carrier Protein Synthase Domain of Module 2 of the Erythromycin Polyketide Synthase" @default.
- W2085143209 cites W1550877969 @default.
- W2085143209 cites W2018210843 @default.
- W2085143209 cites W2045307713 @default.
- W2085143209 cites W2073660800 @default.
- W2085143209 cites W2080279693 @default.
- W2085143209 cites W2120699437 @default.
- W2085143209 doi "https://doi.org/10.1021/bi048147g" @default.
- W2085143209 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15610024" @default.
- W2085143209 hasPublicationYear "2004" @default.
- W2085143209 type Work @default.
- W2085143209 sameAs 2085143209 @default.
- W2085143209 citedByCount "43" @default.
- W2085143209 countsByYear W20851432092012 @default.
- W2085143209 countsByYear W20851432092013 @default.
- W2085143209 countsByYear W20851432092014 @default.
- W2085143209 countsByYear W20851432092015 @default.
- W2085143209 countsByYear W20851432092016 @default.
- W2085143209 countsByYear W20851432092017 @default.
- W2085143209 countsByYear W20851432092020 @default.
- W2085143209 countsByYear W20851432092021 @default.
- W2085143209 countsByYear W20851432092023 @default.
- W2085143209 crossrefType "journal-article" @default.
- W2085143209 hasAuthorship W2085143209A5038399044 @default.
- W2085143209 hasAuthorship W2085143209A5060904695 @default.
- W2085143209 hasAuthorship W2085143209A5081975997 @default.
- W2085143209 hasAuthorship W2085143209A5089983022 @default.
- W2085143209 hasConcept C112243037 @default.
- W2085143209 hasConcept C121332964 @default.
- W2085143209 hasConcept C148898269 @default.
- W2085143209 hasConcept C161790260 @default.
- W2085143209 hasConcept C170493617 @default.
- W2085143209 hasConcept C181199279 @default.
- W2085143209 hasConcept C185592680 @default.
- W2085143209 hasConcept C193557335 @default.
- W2085143209 hasConcept C2780786045 @default.
- W2085143209 hasConcept C553450214 @default.
- W2085143209 hasConcept C55493867 @default.
- W2085143209 hasConcept C62520636 @default.
- W2085143209 hasConcept C71240020 @default.
- W2085143209 hasConcept C74998103 @default.
- W2085143209 hasConcept C93391505 @default.
- W2085143209 hasConceptScore W2085143209C112243037 @default.
- W2085143209 hasConceptScore W2085143209C121332964 @default.
- W2085143209 hasConceptScore W2085143209C148898269 @default.
- W2085143209 hasConceptScore W2085143209C161790260 @default.
- W2085143209 hasConceptScore W2085143209C170493617 @default.
- W2085143209 hasConceptScore W2085143209C181199279 @default.
- W2085143209 hasConceptScore W2085143209C185592680 @default.
- W2085143209 hasConceptScore W2085143209C193557335 @default.
- W2085143209 hasConceptScore W2085143209C2780786045 @default.
- W2085143209 hasConceptScore W2085143209C553450214 @default.
- W2085143209 hasConceptScore W2085143209C55493867 @default.
- W2085143209 hasConceptScore W2085143209C62520636 @default.
- W2085143209 hasConceptScore W2085143209C71240020 @default.
- W2085143209 hasConceptScore W2085143209C74998103 @default.
- W2085143209 hasConceptScore W2085143209C93391505 @default.
- W2085143209 hasIssue "51" @default.
- W2085143209 hasLocation W20851432091 @default.
- W2085143209 hasLocation W20851432092 @default.
- W2085143209 hasOpenAccess W2085143209 @default.
- W2085143209 hasPrimaryLocation W20851432091 @default.
- W2085143209 hasRelatedWork W1570438659 @default.
- W2085143209 hasRelatedWork W1989372630 @default.
- W2085143209 hasRelatedWork W2010860603 @default.
- W2085143209 hasRelatedWork W2048422892 @default.
- W2085143209 hasRelatedWork W2080279693 @default.
- W2085143209 hasRelatedWork W2085143209 @default.
- W2085143209 hasRelatedWork W2087081506 @default.
- W2085143209 hasRelatedWork W264734440 @default.
- W2085143209 hasRelatedWork W2744206599 @default.
- W2085143209 hasRelatedWork W2765426206 @default.
- W2085143209 hasVolume "43" @default.
- W2085143209 isParatext "false" @default.
- W2085143209 isRetracted "false" @default.
- W2085143209 magId "2085143209" @default.
- W2085143209 workType "article" @default.