Informacja

Drogi użytkowniku, aplikacja do prawidłowego działania wymaga obsługi JavaScript. Proszę włącz obsługę JavaScript w Twojej przeglądarce.

Przeglądasz jako GOŚĆ
Tytuł pozycji:

Inhibition of firefly luciferase activity by a HIF prolyl hydroxylase inhibitor.

Tytuł :
Inhibition of firefly luciferase activity by a HIF prolyl hydroxylase inhibitor.
Autorzy :
Günter J; Institute of Physiology, University of Zurich, Zurich, & National Centre of Competence in Research 'Kidney.CH', Zurich, Switzerland.
Wenger RH; Institute of Physiology, University of Zurich, Zurich, & National Centre of Competence in Research 'Kidney.CH', Zurich, Switzerland.
Scholz CC; Institute of Physiology, University of Zurich, Zurich, & National Centre of Competence in Research 'Kidney.CH', Zurich, Switzerland. Electronic address: .
Pokaż więcej
Źródło :
Journal of photochemistry and photobiology. B, Biology [J Photochem Photobiol B] 2020 Sep; Vol. 210, pp. 111980. Date of Electronic Publication: 2020 Jul 27.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Original Publication: Lausanne : Elsevier Sequoia, 1987-
MeSH Terms :
Luciferases, Firefly/*metabolism
Prolyl-Hydroxylase Inhibitors/*chemistry
Animals ; Benzothiazoles/metabolism ; Binding, Competitive ; Fireflies/enzymology ; Glycine/analogs & derivatives ; Glycine/chemistry ; Glycine/metabolism ; Isoquinolines/chemistry ; Isoquinolines/metabolism ; Kinetics ; Luciferases, Firefly/antagonists & inhibitors ; Luciferases, Firefly/genetics ; Prolyl-Hydroxylase Inhibitors/metabolism ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/isolation & purification ; Renilla/enzymology
Contributed Indexing :
Keywords: 2-Oxoglutarate; Dioxygenase; Epigenetics; Erythropoietin; Hypoxia; Kidney disease
Substance Nomenclature :
0 (Benzothiazoles)
0 (D-luciferin)
0 (FG-4592)
0 (Isoquinolines)
0 (Prolyl-Hydroxylase Inhibitors)
0 (Recombinant Proteins)
EC 1.13.12.7 (Luciferases, Firefly)
TE7660XO1C (Glycine)
Entry Date(s) :
Date Created: 20200804 Date Completed: 20210402 Latest Revision: 20210402
Update Code :
20210403
DOI :
10.1016/j.jphotobiol.2020.111980
PMID :
32745950
Czasopismo naukowe
The three hypoxia-inducible factor (HIF) prolyl-4-hydroxylase domain (PHD) 1-3 enzymes confer oxygen sensitivity to the HIF pathway and are novel therapeutic targets for treatment of renal anemia. Inhibition of the PHDs may further be beneficial in other hypoxia-associated diseases, including ischemia and chronic inflammation. Several pharmacologic PHD inhibitors (PHIs) are available, but our understanding of their selectivity and its chemical basis is limited. We here report that the PHI JNJ-42041935 (JNJ-1935) is structurally similar to the firefly luciferase substrate D-luciferin. Our results demonstrate that JNJ-1935 is a novel inhibitor of firefly luciferase enzymatic activity. In contrast, the PHIs FG-4592 (roxadustat) and FG-2216 (ICA, BIQ, IOX3, YM 311) did not affect firefly luciferase. The JNJ-1935 mode of inhibition is competitive with a K i of 1.36 μM. D-luciferin did not inhibit the PHDs, despite its structural similarity to JNJ-1935. This study provides insights into a previously unknown JNJ-1935 off-target effect as well as into the chemical requirements for firefly luciferase and PHD inhibitors and may inform the development of novel compounds targeting these enzymes.
(Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ta witryna wykorzystuje pliki cookies do przechowywania informacji na Twoim komputerze. Pliki cookies stosujemy w celu świadczenia usług na najwyższym poziomie, w tym w sposób dostosowany do indywidualnych potrzeb. Korzystanie z witryny bez zmiany ustawień dotyczących cookies oznacza, że będą one zamieszczane w Twoim komputerze. W każdym momencie możesz dokonać zmiany ustawień dotyczących cookies