Universität zu Köln

Knyphausen, Philipp, de Boor, Susanne, Kuhlmann, Nora, Scislowski, Lukas, Extra, Antje, Baldus, Linda, Schacherl, Magdalena ORCID: 0000-0002-5478-2509, Baumann, Ulrich, Neundorf, Ines ORCID: 0000-0001-6450-3991 and Lammers, Michael ORCID: 0000-0003-4168-4640 (2016). Insights into Lysine Deacetylation of Natively Folded Substrate Proteins by Sirtuins. J. Biol. Chem., 291 (28). S. 14677 - 14695. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

Full text not available from this repository.

Abstract

Sirtuins are NAD(+)-dependent lysine deacylases, regulating a variety of cellular processes. The nuclear Sirt1, the cytosolic Sirt2, and the mitochondrial Sirt3 are robust deacetylases, whereas the other sirtuins have preferences for longer acyl chains. Most previous studies investigated sirtuin-catalyzed deacylation on peptide substrates only. We used the genetic code expansion concept to produce natively folded, site-specific, and lysine-acetylated Sirt1-3 substrate proteins, namely Ras-related nuclear, p53, PEPCK1, superoxide dismutase, cyclophilin D, and Hsp10, and analyzed the deacetylation reaction. Some acetylated proteins such as Ras-related nuclear, p53, and Hsp10 were robustly deacetylated by Sirt1-3. However, other reported sirtuin substrate proteins such as cyclophilin D, superoxide dismutase, and PEPCK1 were not deacetylated. Using a structural and functional approach, we describe the ability of Sirt1-3 to deacetylate two adjacent acetylated lysine residues. The dynamics of this process have implications for the lifetime of acetyl modifications on di-lysine acetylation sites and thus constitute a new mechanism for the regulation of proteins by acetylation. Our studies support that, besides the primary sequence context, the protein structure is a major determinant of sirtuin substrate specificity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knyphausen, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED de Boor, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhlmann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Scislowski, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Extra, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Schacherl, Magdalena UNSPECIFIED orcid.org/0000-0002-5478-2509 UNSPECIFIED Baumann, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, Ines UNSPECIFIED orcid.org/0000-0001-6450-3991 UNSPECIFIED Lammers, Michael UNSPECIFIED orcid.org/0000-0003-4168-4640 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-270006
DOI:	10.1074/jbc.M116.726307
Journal or Publication Title:	J. Biol. Chem.
Volume:	291
Number:	28
Page Range:	S. 14677 - 14695
Date:	2016
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRUCTURAL BASIS; SIRT3-MEDIATED DEACETYLATION; HISTONE DEACETYLASES; STRUCTURE VALIDATION; COREPRESSOR COMPLEX; DIFFRACTION DATA; TRANSGENIC MICE; DRUG TARGET; DNA-BINDING; ADP-RIBOSE Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27000