Naslov
Macrodomain protein from Streptomyces coelicolor - SCO6735 reverses T-linked DNA ADP-ribosylation

Autori
Hloušek-Kasun, Andrea ; Mikolčević, Petra ; Jankevicius, Gytis ; Tromans-Coia, Callum ; Sabljić, Igor ; Bertoša, Branimir ; Ahel, Ivan ; Mikoč, Andreja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
PARP 2019 / Curtin, Nikola ; Corda, Daniela ; Yelamos, Jose ; Bai, Peter - Budimpešta, 2019

Skup
PARP 2019

Mjesto i datum
Budimpešta, Mađarska, 20.05.2019. - 23.05.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
ADP-ribosylation, ADP-ribosyl hydrolase, DNA ADP-ribosylation, Macrodomain, Streptomyces coelicolor

Sažetak
Diverse proteins that constitute ADP- ribosylation metabolic cycle have been found in bacteria from the genus Streptomyces. We focused on the macrodomain family of ADP- ribosyl hydrolases that encompass key players in the recognition, interpretation, and turnover of ADP-ribose signaling. In Streptomyces, ADP-ribosylation is involved in the regulation of morphological differentiation and antibiotic production. Our results on ADP- ribosyl hydrolase from S. coelicolor - SCO6735 showed that disruption of SCO6735 increases production of antibiotic actinorhodin. We structurally and biochemically characterized SCO6735 protein. The crystal structure of SCO6735 revealed highly conserved three- layered α-β-α sandwich macrodomain fold with a deep cleft that represents a putative ligand- binding site. Currently, we are employing different molecular modelling methods in order to pinpoint catalytic mechanism of SCO6735 protein. Experiments in vitro showed that SCO6735 is active on both protein and DNA modified substrates ; it efficiently reverses protein ADP-ribosylation on glutamate residues and DNA ADP-ribosylation on thymidines that have been modified by DarT toxin. SCO6735 activity in vivo has been shown in E. coli ; when SCO6735 and DarT are co-expressed, SCO6735 can rescue E. coli from the toxic effect of DarT.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Biotehnologija

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