caa a22 4500 46793875X CHVBK 20180406153005.0 cr unu---uuuuu 170328e20060901xx s 000 0 eng 10.1007/s10822-006-9084-9 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9084-9 Comparative and pharmacophore model for deacetylase SIRT1 [Elektronische Daten] [Tero Huhtiniemi, Carsten Wittekindt, Tuomo Laitinen, Jukka Leppänen, Antero Salminen, Antti Poso, Maija Lahtela-Kakkonen] Sirtuins are NAD-dependent histone deacetylases, which cleave the acetyl-group from acetylated proteins, such as histones but also the acetyl groups from several transcription factors, and in this way can change their activities. Of all seven mammalian SirTs, the human sirtuin SirT1 has been the most extensively studied. However, there is no crystal structure or comparative model reported for SirT1. We have therefore built up a three-dimensional comparison model of the SirT1 protein catalytic core (domain area from residues 244 to 498 of the full length SirT1) in order to assist in the investigation of active site-ligand interactions and in the design of novel SirT1 inhibitors. In this study we also propose the binding-mode of recently reported set of indole-based inhibitors in SirT1. The site of interaction and the ligand conformation were predicted by the use of molecular docking techniques. To distinguish between active and inactive compounds, a post-docking filter based on H-bond network was constructed. Docking results were used to investigate the pharmacophore and to identify a filter for database mining. Springer Science+Business Media, LLC, 2006 Comparative modelling nationallicence Computational docking nationallicence NAD-dependent deacetylation nationallicence Pharmacophore nationallicence Sir2 nationallicence SirT1 nationallicence Sirtuins nationallicence Huhtiniemi Tero Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut Wittekindt Carsten Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut Laitinen Tuomo Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut Leppänen Jukka Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut Salminen Antero Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut Poso Antti Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut Lahtela-Kakkonen Maija Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/9(2006-09-01), 589-599 0920-654X 20:9<589 2006 20 10822 https://doi.org/10.1007/s10822-006-9084-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9084-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Huhtiniemi Tero Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Wittekindt Carsten Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Laitinen Tuomo Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Leppänen Jukka Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Salminen Antero Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Poso Antti Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Lahtela-Kakkonen Maija Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/9(2006-09-01), 589-599 0920-654X 20:9<589 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer