FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000730671> ?p ?o ?g. }

• W2000730671 endingPage "25315" @default.
• W2000730671 startingPage "25305" @default.
• W2000730671 abstract "Human pyruvate dehydrogenase complex (PDC) is down-regulated by pyruvate dehydrogenase kinase (PDK) isoforms 1-4. PDK4 is overexpressed in skeletal muscle in type 2 diabetes, resulting in impaired glucose utilization. Here we show that human PDK4 has robust core-free basal activity, which is considerably higher than activity levels of other PDK isoforms stimulated by the PDC core. PDK4 binds the L3 lipoyl domain, but its activity is not significantly stimulated by any individual lipoyl domains or the core of PDC. The 2.0-A crystal structures of the PDK4 dimer with bound ADP reveal an open conformation with a wider active-site cleft, compared with that in the closed conformation epitomized by the PDK2-ADP structure. The open conformation in PDK4 shows partially ordered C-terminal cross-tails, in which the conserved DW (Asp(394)-Trp(395)) motif from one subunit anchors to the N-terminal domain of the other subunit. The open conformation fosters a reduced binding affinity for ADP, facilitating the efficient removal of product inhibition by this nucleotide. Alteration or deletion of the DW-motif disrupts the C-terminal cross-tail anchor, resulting in the closed conformation and the nearly complete inactivation of PDK4. Fluorescence quenching and enzyme activity data suggest that compounds AZD7545 and dichloroacetate lock PDK4 in the open and the closed conformational states, respectively. We propose that PDK4 with bound ADP exists in equilibrium between the open and the closed conformations. The favored metastable open conformation is responsible for the robust basal activity of PDK4 in the absence of the PDC core." @default.
• W2000730671 created "2016-06-24" @default.
• W2000730671 creator A5012092032 @default.
• W2000730671 creator A5027835055 @default.
• W2000730671 creator A5038727241 @default.
• W2000730671 creator A5046753083 @default.
• W2000730671 creator A5077177876 @default.
• W2000730671 creator A5082759219 @default.
• W2000730671 date "2008-09-01" @default.
• W2000730671 modified "2023-10-02" @default.
• W2000730671 title "Pyruvate Dehydrogenase Kinase-4 Structures Reveal a Metastable Open Conformation Fostering Robust Core-free Basal Activity" @default.
• W2000730671 cites W1517812011 @default.
• W2000730671 cites W1539796472 @default.
• W2000730671 cites W1608213028 @default.
• W2000730671 cites W170698896 @default.
• W2000730671 cites W1757455318 @default.
• W2000730671 cites W1832257936 @default.
• W2000730671 cites W1885970184 @default.
• W2000730671 cites W1964416938 @default.
• W2000730671 cites W1965548069 @default.
• W2000730671 cites W1966553114 @default.
• W2000730671 cites W1973713633 @default.
• W2000730671 cites W1975171610 @default.
• W2000730671 cites W1975333713 @default.
• W2000730671 cites W1985085712 @default.
• W2000730671 cites W1985629904 @default.
• W2000730671 cites W1985748618 @default.
• W2000730671 cites W1986407336 @default.
• W2000730671 cites W1998093640 @default.
• W2000730671 cites W1998824954 @default.
• W2000730671 cites W2001641653 @default.
• W2000730671 cites W2001958358 @default.
• W2000730671 cites W2007829111 @default.
• W2000730671 cites W2009381958 @default.
• W2000730671 cites W2011646732 @default.
• W2000730671 cites W2016505307 @default.
• W2000730671 cites W2016748909 @default.
• W2000730671 cites W2020257412 @default.
• W2000730671 cites W2029722877 @default.
• W2000730671 cites W2037205798 @default.
• W2000730671 cites W2038840577 @default.
• W2000730671 cites W2039446355 @default.
• W2000730671 cites W2039903160 @default.
• W2000730671 cites W2041096022 @default.
• W2000730671 cites W2043648447 @default.
• W2000730671 cites W2045371106 @default.
• W2000730671 cites W2050961213 @default.
• W2000730671 cites W2053291546 @default.
• W2000730671 cites W2053815283 @default.
• W2000730671 cites W2059228937 @default.
• W2000730671 cites W2060268336 @default.
• W2000730671 cites W2060809301 @default.
• W2000730671 cites W2061266943 @default.
• W2000730671 cites W2062838148 @default.
• W2000730671 cites W2076300945 @default.
• W2000730671 cites W2076812146 @default.
• W2000730671 cites W2083539959 @default.
• W2000730671 cites W2084295225 @default.
• W2000730671 cites W2092131410 @default.
• W2000730671 cites W2106882534 @default.
• W2000730671 cites W2108294918 @default.
• W2000730671 cites W2115243233 @default.
• W2000730671 cites W2125634299 @default.
• W2000730671 cites W2136611430 @default.
• W2000730671 cites W2138710796 @default.
• W2000730671 cites W2142735739 @default.
• W2000730671 cites W2144285975 @default.
• W2000730671 cites W2146394845 @default.
• W2000730671 cites W2153938802 @default.
• W2000730671 cites W2160695434 @default.
• W2000730671 cites W2166679041 @default.
• W2000730671 cites W2167123876 @default.
• W2000730671 cites W2182463865 @default.
• W2000730671 cites W2496709319 @default.
• W2000730671 cites W4233270123 @default.
• W2000730671 doi "https://doi.org/10.1074/jbc.m802249200" @default.
• W2000730671 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2533096" @default.
• W2000730671 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18658136" @default.
• W2000730671 hasPublicationYear "2008" @default.
• W2000730671 type Work @default.
• W2000730671 sameAs 2000730671 @default.
• W2000730671 citedByCount "66" @default.
• W2000730671 countsByYear W20007306712012 @default.
• W2000730671 countsByYear W20007306712013 @default.
• W2000730671 countsByYear W20007306712014 @default.
• W2000730671 countsByYear W20007306712015 @default.
• W2000730671 countsByYear W20007306712016 @default.
• W2000730671 countsByYear W20007306712017 @default.
• W2000730671 countsByYear W20007306712018 @default.
• W2000730671 countsByYear W20007306712019 @default.
• W2000730671 countsByYear W20007306712020 @default.
• W2000730671 countsByYear W20007306712021 @default.
• W2000730671 countsByYear W20007306712022 @default.
• W2000730671 countsByYear W20007306712023 @default.
• W2000730671 crossrefType "journal-article" @default.
• W2000730671 hasAuthorship W2000730671A5012092032 @default.
• W2000730671 hasAuthorship W2000730671A5027835055 @default.
• W2000730671 hasAuthorship W2000730671A5038727241 @default.

• next