Matches in SemOpenAlex for { <https://semopenalex.org/work/W2138437172> ?p ?o ?g. }
Showing items 1 to 95 of
95
with 100 items per page.
- W2138437172 endingPage "53" @default.
- W2138437172 startingPage "44" @default.
- W2138437172 abstract "Xanthine/alpha-ketoglutarate (alphaKG) dioxygenase (XanA) is a non-heme mononuclear Fe(II) enzyme that decarboxylates alphaKG to succinate and CO(2) while hydroxylating xanthine to generate uric acid. In the absence of a XanA crystal structure, a homology model was used to target several putative active site residues for mutagenesis. Wild-type XanA and ten enzyme variants were purified from recombinant Escherichia coli cells and characterized. The H149A and D151A variants were inactive and the H340A variant exhibited only 0.17% of the wild-type enzyme activity, consistent with the proposed role of His149, Asp151, and His340 as Fe ligands. The K122A variant led to a 2-fold increase in the K(d) of alphaKG as measured by fluorescence quenching analysis, in agreement with Lys122 acting to stabilize the binding of alphaKG. The N358A variant exhibited a 23-fold decrease in k(cat)/K(m) compared to wild-type XanA, pointing to a key role of Asn358 in catalysis. 9-Methylxanthine was exploited as an alternate substrate, and the C357A, E137A, and D138A variants were found to exhibit relatively enhanced activity consistent with Cys357, Glu137, and Asp138 being proximal to N-9 or involved in its proper positioning. 6,8-Dihydroxypurine was identified as a slow-binding competitive inhibitor of XanA, and significant decreases (E137A and D138A) or increases (Q356A and N358A) in K(i)(app) of the variants were interpreted in terms of distinct interactions between this compound and the corresponding active site side chains. Further support for Cys357 residing at the active site was obtained using thiol-specific reagents that inactivated wild-type enzyme (with partial protection by substrate), whereas the C357A variant was resistant to these reagents. The Q101A, Q356A, and C357A variants showed elevated ferroxidase activity in the absence of substrates, pointing to the presence of the corresponding side chains at the active site. These results confirm most aspects of the homology model and provide additional insight into the enzyme reactivity." @default.
- W2138437172 created "2016-06-24" @default.
- W2138437172 creator A5031062990 @default.
- W2138437172 creator A5065700590 @default.
- W2138437172 creator A5067007014 @default.
- W2138437172 creator A5087592842 @default.
- W2138437172 date "2008-02-01" @default.
- W2138437172 modified "2023-09-26" @default.
- W2138437172 title "Characterization of active site variants of xanthine hydroxylase from Aspergillus nidulans" @default.
- W2138437172 cites W1933585739 @default.
- W2138437172 cites W1985564974 @default.
- W2138437172 cites W1988722320 @default.
- W2138437172 cites W1991107732 @default.
- W2138437172 cites W1998967175 @default.
- W2138437172 cites W2018936532 @default.
- W2138437172 cites W2028049009 @default.
- W2138437172 cites W2047276432 @default.
- W2138437172 cites W2048935114 @default.
- W2138437172 cites W2053850636 @default.
- W2138437172 cites W2066414785 @default.
- W2138437172 cites W2092025571 @default.
- W2138437172 cites W2122660082 @default.
- W2138437172 cites W2128586767 @default.
- W2138437172 doi "https://doi.org/10.1016/j.abb.2007.11.002" @default.
- W2138437172 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2258140" @default.
- W2138437172 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18036331" @default.
- W2138437172 hasPublicationYear "2008" @default.
- W2138437172 type Work @default.
- W2138437172 sameAs 2138437172 @default.
- W2138437172 citedByCount "10" @default.
- W2138437172 countsByYear W21384371722014 @default.
- W2138437172 countsByYear W21384371722015 @default.
- W2138437172 countsByYear W21384371722017 @default.
- W2138437172 countsByYear W21384371722021 @default.
- W2138437172 countsByYear W21384371722023 @default.
- W2138437172 crossrefType "journal-article" @default.
- W2138437172 hasAuthorship W2138437172A5031062990 @default.
- W2138437172 hasAuthorship W2138437172A5065700590 @default.
- W2138437172 hasAuthorship W2138437172A5067007014 @default.
- W2138437172 hasAuthorship W2138437172A5087592842 @default.
- W2138437172 hasBestOaLocation W21384371722 @default.
- W2138437172 hasConcept C103408237 @default.
- W2138437172 hasConcept C104317684 @default.
- W2138437172 hasConcept C107824862 @default.
- W2138437172 hasConcept C143065580 @default.
- W2138437172 hasConcept C16318435 @default.
- W2138437172 hasConcept C181199279 @default.
- W2138437172 hasConcept C185592680 @default.
- W2138437172 hasConcept C207583985 @default.
- W2138437172 hasConcept C2776834422 @default.
- W2138437172 hasConcept C2776923806 @default.
- W2138437172 hasConcept C2779470414 @default.
- W2138437172 hasConcept C41183919 @default.
- W2138437172 hasConcept C547475151 @default.
- W2138437172 hasConcept C55493867 @default.
- W2138437172 hasConcept C71240020 @default.
- W2138437172 hasConceptScore W2138437172C103408237 @default.
- W2138437172 hasConceptScore W2138437172C104317684 @default.
- W2138437172 hasConceptScore W2138437172C107824862 @default.
- W2138437172 hasConceptScore W2138437172C143065580 @default.
- W2138437172 hasConceptScore W2138437172C16318435 @default.
- W2138437172 hasConceptScore W2138437172C181199279 @default.
- W2138437172 hasConceptScore W2138437172C185592680 @default.
- W2138437172 hasConceptScore W2138437172C207583985 @default.
- W2138437172 hasConceptScore W2138437172C2776834422 @default.
- W2138437172 hasConceptScore W2138437172C2776923806 @default.
- W2138437172 hasConceptScore W2138437172C2779470414 @default.
- W2138437172 hasConceptScore W2138437172C41183919 @default.
- W2138437172 hasConceptScore W2138437172C547475151 @default.
- W2138437172 hasConceptScore W2138437172C55493867 @default.
- W2138437172 hasConceptScore W2138437172C71240020 @default.
- W2138437172 hasIssue "1" @default.
- W2138437172 hasLocation W21384371721 @default.
- W2138437172 hasLocation W21384371722 @default.
- W2138437172 hasLocation W21384371723 @default.
- W2138437172 hasLocation W21384371724 @default.
- W2138437172 hasOpenAccess W2138437172 @default.
- W2138437172 hasPrimaryLocation W21384371721 @default.
- W2138437172 hasRelatedWork W1974993927 @default.
- W2138437172 hasRelatedWork W1995916976 @default.
- W2138437172 hasRelatedWork W2017218857 @default.
- W2138437172 hasRelatedWork W2047434710 @default.
- W2138437172 hasRelatedWork W2062629157 @default.
- W2138437172 hasRelatedWork W2070681424 @default.
- W2138437172 hasRelatedWork W2138437172 @default.
- W2138437172 hasRelatedWork W258580054 @default.
- W2138437172 hasRelatedWork W2792698313 @default.
- W2138437172 hasRelatedWork W624538068 @default.
- W2138437172 hasVolume "470" @default.
- W2138437172 isParatext "false" @default.
- W2138437172 isRetracted "false" @default.
- W2138437172 magId "2138437172" @default.
- W2138437172 workType "article" @default.