title: Disruption of Macrodomain Protein SCO6735 Increases Antibiotic Production in Streptomyces coelicolor.
abstract: ADP-ribosylation is a post-translational modification that can alter the physical and chemical properties of target proteins and that controls many important cellular processes. Macrodomains are evolutionarily conserved structural domains that bind ADP-ribose derivatives and are found in proteins with diverse cellular functions. Some proteins from the macrodomain family can hydrolyze ADP-ribosylated substrates and therefore reverse this post-translational modification. Bacteria and Streptomyces, in particular, are known to utilize protein ADP-ribosylation, yet very little is known about their enzymes that synthesize and remove this modification. We have determined the crystal structure and characterized, both biochemically and functionally, the macrodomain protein SCO6735 from Streptomyces coelicolor This protein is a member of an uncharacterized subfamily of macrodomain proteins. Its crystal structure revealed a highly conserved macrodomain fold. We showed that SCO6735 possesses the ability to hydrolyze PARP-dependent protein ADP-ribosylation. Furthermore, we showed that expression of this protein is induced upon DNA damage and that deletion of this protein in S. coelicolor increases antibiotic production. Our results provide the first insights into the molecular basis of its action and impact on Streptomyces metabolism.
authors.affiliation: From the Division of Molecular Biology.
authors.forename: Jasna
authors.initials: J
authors.lastname: Lalić
authors.affiliation: From the Division of Molecular Biology.
authors.forename: Melanija
authors.initials: M
authors.lastname: Posavec Marjanović
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Palazzo
authors.affiliation: From the Division of Molecular Biology.
authors.forename: Dragutin
authors.initials: D
authors.lastname: Perina
authors.affiliation: the Division of Physical Chemistry, and.
authors.forename: Igor
authors.initials: I
authors.lastname: Sabljić
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.|the Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb 10002, Croatia.
authors.forename: Roko
authors.initials: R
authors.lastname: Žaja
authors.affiliation: the Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany, and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Colby
authors.affiliation: From the Division of Molecular Biology.
authors.forename: Bruna
authors.initials: B
authors.lastname: Pleše
authors.affiliation: From the Division of Molecular Biology.
authors.forename: Mirna
authors.initials: M
authors.lastname: Halasz
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Gytis
authors.initials: G
authors.lastname: Jankevicius
authors.affiliation: the School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Moulsecoomb, Brighton BN2 4GJ, United Kingdom.
authors.forename: Giselda
authors.initials: G
authors.lastname: Bucca
authors.affiliation: the Division for Marine and Environmental Research, Ruđer Bošković Institute, Zagreb 10002, Croatia.
authors.forename: Marijan
authors.initials: M
authors.lastname: Ahel
authors.affiliation: the Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany, and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Matić
authors.affiliation: From the Division of Molecular Biology.
authors.forename: Helena
authors.initials: H
authors.lastname: Ćetković
authors.affiliation: the Division of Physical Chemistry, and.
authors.forename: Marija
authors.initials: M
authors.lastname: Luić
authors.affiliation: From the Division of Molecular Biology, mikoc@irb.hr.
authors.forename: Andreja
authors.initials: A
authors.lastname: Mikoč
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom, ivan.ahel@path.ox.ac.uk.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ahel
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D011499:Protein Processing, Post-Translational; D048372:Streptomyces coelicolor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000246:Adenosine Diphosphate Ribose
keywords: ADP-ribose; ADP-ribosylation; DNA damage; PARP; Streptomyces; antibiotics; enzyme mechanism; microbiology; nicotinamide adenine dinucleotide (NAD); post-translational modification (PTM)