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Pregled bibliografske jedinice broj: 676260

Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo- glycohydrolase activities


Barkauskaite, Eva; Brassington, Amy; Tan, Edwin S.; Warwicker, Jim; Dunstan, Mark S.; Banos, Benito; Lafite, Pierre; Ahel, Marijan; Mitchison, Timothy J.; Ahel, Ivan; Leys, David
Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo- glycohydrolase activities // Nature communications, 4 (2013), 2164-1 doi:10.1038/ncomms3164 (međunarodna recenzija, članak, znanstveni)


Naslov
Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo- glycohydrolase activities

Autori
Barkauskaite, Eva ; Brassington, Amy ; Tan, Edwin S. ; Warwicker, Jim ; Dunstan, Mark S. ; Banos, Benito ; Lafite, Pierre ; Ahel, Marijan ; Mitchison, Timothy J. ; Ahel, Ivan ; Leys, David

Izvornik
Nature communications (2041-1723) 4 (2013); 2164-1

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Glycosidase; poly(adenosine diphosphate ribose)

Sažetak
Poly-ADP-ribosylation is a post-translational modification that regulates processes involved in genome stability. Breakdown of the poly(ADP- ribose) (PAR) polymer is catalysed by poly(ADP- ribose) glycohydrolase (PARG), whose endo- glycohydrolase activity generates PAR fragments. Here we present the crystal structure of PARG incorporating the PAR substrate. The two terminal ADP-ribose units of the polymeric substrate are bound in exo-mode. Biochemical and modelling studies reveal that PARG acts predominantly as an exo- glycohydrolase. This preference is linked to Phe902 (human numbering), which is responsible for low-affinity binding of the substrate in endo-mode. Our data reveal the mechanism of poly- ADP-ribosylation reversal, with ADP- ribose as the dominant product, and suggest that the release of apoptotic PAR fragments occurs at unusual PAR/PARG ratios.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Projekt / tema
098-0982934-2712 - Organski spojevi kao molekulski obilježivači antropogenog utjecaja na okoliš (Marijan Ahel, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Autor s matičnim brojem:
Marijan Ahel, (145)
Ivan Ahel, (235841)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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