FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2974248045> ?p ?o ?g. }

• W2974248045 abstract "Abstract Human phenylalanine hydroxylase (hPAH) hydroxylates l -phenylalanine ( l -Phe) to l -tyrosine, a precursor for neurotransmitter biosynthesis. Phenylketonuria (PKU), caused by mutations in PAH that impair PAH function, leads to neurological impairment when untreated. Understanding the hPAH structural and regulatory properties is essential to outline PKU pathophysiological mechanisms. Each hPAH monomer comprises an N-terminal regulatory, a central catalytic and a C-terminal oligomerisation domain. To maintain physiological l -Phe levels, hPAH employs complex regulatory mechanisms. Resting PAH adopts an auto-inhibited conformation where regulatory domains block access to the active site. l -Phe-mediated allosteric activation induces a repositioning of the regulatory domains. Since a structure of activated wild-type hPAH is lacking, we addressed hPAH l -Phe-mediated conformational changes and report the first solution structure of the allosterically activated state. Our solution structures obtained by small-angle X-ray scattering support a tetramer with distorted P222 symmetry, where catalytic and oligomerisation domains form a core from which regulatory domains protrude, positioning themselves close to the active site entrance in the absence of l -Phe. Binding of l -Phe induces a large movement and dimerisation of regulatory domains, exposing the active site. Activated hPAH is more resistant to proteolytic cleavage and thermal denaturation, suggesting that the association of regulatory domains stabilises hPAH." @default.
• W2974248045 created "2019-09-26" @default.
• W2974248045 creator A5015641575 @default.
• W2974248045 creator A5016343135 @default.
• W2974248045 creator A5023420541 @default.
• W2974248045 creator A5032818232 @default.
• W2974248045 creator A5057380825 @default.
• W2974248045 creator A5065807435 @default.
• W2974248045 creator A5071421456 @default.
• W2974248045 creator A5087502848 @default.
• W2974248045 date "2019-09-20" @default.
• W2974248045 modified "2023-10-15" @default.
• W2974248045 title "Structure of full-length wild-type human phenylalanine hydroxylase by small angle X-ray scattering reveals substrate-induced conformational stability" @default.
• W2974248045 cites W1097995217 @default.
• W2974248045 cites W1481617035 @default.
• W2974248045 cites W1793877278 @default.
• W2974248045 cites W1829864290 @default.
• W2974248045 cites W1868339174 @default.
• W2974248045 cites W1972662391 @default.
• W2974248045 cites W1978584239 @default.
• W2974248045 cites W1982126789 @default.
• W2974248045 cites W1986751844 @default.
• W2974248045 cites W1995586409 @default.
• W2974248045 cites W1996106128 @default.
• W2974248045 cites W2014444112 @default.
• W2974248045 cites W2027589959 @default.
• W2974248045 cites W2030599632 @default.
• W2974248045 cites W2041728208 @default.
• W2974248045 cites W2045884770 @default.
• W2974248045 cites W2049042424 @default.
• W2974248045 cites W2049972320 @default.
• W2974248045 cites W2050091361 @default.
• W2974248045 cites W2056342195 @default.
• W2974248045 cites W2066088601 @default.
• W2974248045 cites W2070404310 @default.
• W2974248045 cites W2072674961 @default.
• W2974248045 cites W2074420589 @default.
• W2974248045 cites W2076727938 @default.
• W2974248045 cites W2085216601 @default.
• W2974248045 cites W2085899620 @default.
• W2974248045 cites W2088472096 @default.
• W2974248045 cites W2096607326 @default.
• W2974248045 cites W2106776097 @default.
• W2974248045 cites W2117560166 @default.
• W2974248045 cites W2124983865 @default.
• W2974248045 cites W2131858055 @default.
• W2974248045 cites W2136967346 @default.
• W2974248045 cites W2140338457 @default.
• W2974248045 cites W2151207180 @default.
• W2974248045 cites W2164361934 @default.
• W2974248045 cites W2166816916 @default.
• W2974248045 cites W2275975686 @default.
• W2974248045 cites W2278468495 @default.
• W2974248045 cites W2329080044 @default.
• W2974248045 cites W2345449302 @default.
• W2974248045 cites W2477433726 @default.
• W2974248045 cites W2627034197 @default.
• W2974248045 cites W2707646777 @default.
• W2974248045 cites W2761810763 @default.
• W2974248045 cites W2781364521 @default.
• W2974248045 cites W2913315318 @default.
• W2974248045 doi "https://doi.org/10.1038/s41598-019-49944-x" @default.
• W2974248045 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6754429" @default.
• W2974248045 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31541188" @default.
• W2974248045 hasPublicationYear "2019" @default.
• W2974248045 type Work @default.
• W2974248045 sameAs 2974248045 @default.
• W2974248045 citedByCount "13" @default.
• W2974248045 countsByYear W29742480452020 @default.
• W2974248045 countsByYear W29742480452021 @default.
• W2974248045 countsByYear W29742480452022 @default.
• W2974248045 countsByYear W29742480452023 @default.
• W2974248045 crossrefType "journal-article" @default.
• W2974248045 hasAuthorship W2974248045A5015641575 @default.
• W2974248045 hasAuthorship W2974248045A5016343135 @default.
• W2974248045 hasAuthorship W2974248045A5023420541 @default.
• W2974248045 hasAuthorship W2974248045A5032818232 @default.
• W2974248045 hasAuthorship W2974248045A5057380825 @default.
• W2974248045 hasAuthorship W2974248045A5065807435 @default.
• W2974248045 hasAuthorship W2974248045A5071421456 @default.
• W2974248045 hasAuthorship W2974248045A5087502848 @default.
• W2974248045 hasBestOaLocation W29742480451 @default.
• W2974248045 hasConcept C12554922 @default.
• W2974248045 hasConcept C161790260 @default.
• W2974248045 hasConcept C166342909 @default.
• W2974248045 hasConcept C181199279 @default.
• W2974248045 hasConcept C185592680 @default.
• W2974248045 hasConcept C207009774 @default.
• W2974248045 hasConcept C2777431362 @default.
• W2974248045 hasConcept C2778886173 @default.
• W2974248045 hasConcept C41183919 @default.
• W2974248045 hasConcept C47701112 @default.
• W2974248045 hasConcept C515207424 @default.
• W2974248045 hasConcept C55493867 @default.
• W2974248045 hasConcept C71240020 @default.
• W2974248045 hasConcept C8010536 @default.
• W2974248045 hasConcept C86803240 @default.
• W2974248045 hasConceptScore W2974248045C12554922 @default.
• W2974248045 hasConceptScore W2974248045C161790260 @default.
• W2974248045 hasConceptScore W2974248045C166342909 @default.

• next