Structure-based development of an affinity probe for sirtuin 2
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Tartalom: http://real.mtak.hu/34687/
Archívum: REAL
Gyűjtemény: Status = Published
Subject = R Medicine / orvostudomány: RM Therapeutics. Pharmacology / terápia, gyógyszertan
Subject = Q Science / természettudomány: QH Natural history / természetrajz: QH301 Biology / biológia: QH3015 Molecular biology / molekuláris biológia
Type = Article
Cím:
Structure-based development of an affinity probe for sirtuin 2
Létrehozó:
Schiedel, M.
Rumpf, T.
Karaman, B.
Lehotzky, Attila
Gerhardt, S.
Ovádi, Judit
Dátum:
2016
Téma:
QH3015 Molecular biology / molekuláris biológia
RM Therapeutics. Pharmacology / terápia, gyógyszertan
Tartalmi leírás:
Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl groups, as well as other acyl groups, from the É?-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, thus making Sirt2 a promising target for pharmaceutical intervention. Here, based on a crystal structure of Sirt2 in complex with an optimized sirtuin rearranging ligand (SirReal) that shows improved potency, water solubility, and cellular efficacy, we present the development of the first Sirt2-selective affinity probe. A slow dissociation of the probe/enzyme complex offers new applications for SirReals, such as biophysical characterization, fragment-based screening, and affinity pull-down assays. This possibility makes the SirReal probe an important tool for studying sirtuin biology. A new probe for drug design: An affinity probe for Sirt2 has been developed that shows excellent selectivity and potency. The slow dissociation rate of the enzyme-ligand complex enables new applications, such as biolayer interferometry, and pull-down assays for sirtuin rearranging ligands. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Schiedel, M. and Rumpf, T. and Karaman, B. and Lehotzky, Attila and Gerhardt, S. and Ovádi, Judit (2016) Structure-based development of an affinity probe for sirtuin 2. ANGEWANDTE CHEMIE INTERNATIONAL EDITION, 55 (6). pp. 2252-2256. ISSN 1433-7851
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