Human sirtuins: Structures and flexibility

Sacconnay, Lionel; Carrupt, Pierre‐Alain; Nurisso, Alessandra

doi:10.1016/j.jsb.2016.10.008

Cited by 36 publications

(33 citation statements)

References 66 publications

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“…Sirtuins may thus be distinguishable by their diverse subcellular localizations. SIRT1, SIRT6, and SIRT7 are mainly located in the nucleus [5,6], while SIRT3, SIRT4, and SIRT5 are mainly located in the mitochondria. SIRT1 and SIRT5 have been found in the cytoplasm [3,7].…”

Section: Overview Of the Sirtuin Familymentioning

confidence: 99%

The Roles of Sirtuin Family Proteins in Cancer Progression

Zhao

Hou

et al. 2019

Cancers

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Sirtuin family members are characterized by either mono-ADP-ribosyltransferase or deacylase activity and are linked to various cancer-related biological pathways as regulators of transcriptional progression. Sirtuins play fundamental roles in carcinogenesis and maintenance of the malignant phenotype, mainly participating in cancer cell viability, apoptosis, metastasis, and tumorigenesis. Although sirtuin family members have a high degree of homology, they may play different roles in various kinds of cancer. This review highlights their fundamental roles in tumorigenesis and cancer development and provides a critical discussion of their dual roles in cancer, namely, as tumor promoters or tumor suppressors.

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Section: Overview Of the Sirtuin Familymentioning

confidence: 99%

The Roles of Sirtuin Family Proteins in Cancer Progression

Zhao

Hou

et al. 2019

Cancers

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“…Resveratrol is an activator of Sirt1 [33][34][35][36][37][38]. Whether does resveratrol activate the Shh signaling via Sirt1?…”

Section: Discussionmentioning

confidence: 99%

“…Activated Sirt1 by resveratrol has anti-aging, neuroprotective and neurogenetic and anti-hypertrophic scar effects [33][34][35][36][37][38][39]. Tiberi et al reported that BCL6/BCOR/SIRT1 complex inhibited medulloblastoma and enhanced neurogenesis by suppressing the Shh signaling [40].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Activated Sonic Hedgehog Signaling to Enhance Viability of NIH3T3 Cells in Vitro via Regulation of Sirt1

Guo¹,

Liao²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Injuries of the brain and spinal cord result in the formation of glial (reactive gliosis) and fibrotic (formed by fibroblasts) scars. Recent studies have shown that the fibrotic scar was much more important for hindering regeneration after brain or spinal cord injury than the astrocytic scar. However, it has been given much less attention for effects and mechanism of fibroblasts during formation of the fibrotic scar. Resveratrol may be a potential anti-scarring agent in burn-related scarring and keloid fibroblasts. However, it is unclear whether and how resveratrol affects formation of the fibrotic scar after brain or spinal cord injury. Earlier studies have shown that the activated Shh signaling has anti-apoptosis, anti-oxidation, anti-inflammation properties. Moreover, resveratrol can activate the Shh signaling. However, it is unclear how resveratrol activates the Shh signaling. Resveratrol is a activator of Sirt1. It is unknown whether resveratrol activates the Shh signaling via Sirt1. Methods: NIH3T3 cells, a fibroblast cell line, were used as model cells and treated with drugs. Cell viability was assessed by Cell Counting Kit 8. The expressions and activity of Shh signaling pathway proteins were evaluated by immunocytochemistry and Western blotting. Transcriptional activity of Gli-1 was detected with Dual-Luciferase Reporter Gene Assay Kit. Results: Resveratrol, Sirt1 agonist STR1720 and recombinant mouse Shh protein, an activator of hedgehog signaling, enhanced the viability of NIH3T3 cells, promoted Smo to translocated to the primary cilia and Gli-1 entered into the nuclei from cytoplasm, and upregulated expressions of Shh, Ptc-1, Smo, and Gli-1 proteins, which can be reversed by Smo antagonist cyclopamine and Sirt1 antagonist Sirtinol. Additionally, resveratrol increased transcriptional activity of Gli-1. Conclusion: We indicate in the first time that it may be mediated by Sirt1 for resveratrol activating the Shh signaling to enhance viability of NIH3T3 cells, and Sirt1 may be a regulator for upstream of the Shh signaling pathway.This study provides a basis for further investigating effects and mechanism of resveratrol during the formation of fibrous scar after brain or spinal cord injury.

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“…After the balanced system was observed, production was continued for 50 ns. The ptraj program from AmberTools and VMD was used to perform trajectory analysis of the molecular dynamic simulation results [15]. The parameters analyzed were RMSD and root mean square fluctuation (RMSF), and the hydrogen bond conditions were analyzed using VMD program.…”

Section: Molecular Dynamicsmentioning

confidence: 99%

“…Therefore, the present study used an in silico study with molecular docking and dynamic simulations of the SIRT1 enzyme (PDB IDs 4ZZI, 4ZZJ, 4ZZH, and 5BTR) to determine the bonding interactions of SIRT1 required for ligand selectivity and selective identification of bond interactions and target bond interactions with biological function [14,15].…”

Section: Introductionmentioning

confidence: 99%

In Silico Study of Sirt1 Activators Using a Molecular Dynamic Approach

Azminah

Radji²,

Mun’im

et al. 2019

Int J App Pharm

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Objective: The importance of SIRT1 activator’s role in antidiabetic and anti-aging therapies is widely demonstrated. Drug discovery and developmentare time consuming. Drug design can be performed in silico using molecular dynamic approaches to accelerate and facilitate identification of the bestcompound candidates and their physicochemical characteristics and hit-to-lead selection.Methods: In silico study of SIRT1 activator for complexes using of Protein Data Bank (PDB) IDs 4ZZI, 4ZZJ 4ZZH, and 5BTR and 4TO ligand. Ligand–receptor interactions and bond energies were determined using molecular docking with the AutoDock4Zn program. Then, the complex with thebest bond energy was identified using a simulation of the molecular dynamics (50 ns) using the Amber program, and values for root mean squaredeviation, root mean square fluctuation, and bond energy were determined using the Molecular Mechanic–Poisson Boltzmann (Generalized Born)surface area (MM-PB[GB]SA) calculation.Results: Interaction analysis between activator ligand (4TO) and the SIRT1 receptor (PDB IDs 4ZZJ and 5BTR) revealed the ligand’s selectivity forhydrophobic interaction at Leu206, Ile223, Ile227, and hydrophilic interaction at Asn226, Glu230. Hydrogen bond interactions between Glu230 and Arg234(allosteric region) with Arg446, Val459, His473, and Asp475 (catalytic region) brought them close to the bounding substrate area. Bond energy valuesobtained using the MM-GB(PB)SA calculation showed 4TO interaction with 4ZZJ (MMGBSA ΔG, −31.4729–−26.6756; MMPBSA ΔG, −32.6292–−28.486].The bond energy value of the 4TO interaction with 5BTR showed MMGBSA ΔG = −40.6255–−30.0653 and MMPBSA ΔG = −34.6713–−25.9951.Conclusions: These findings provide important information on the target interaction of the bonds to the more selective SIRT1 activator useful fordrug discovery and development.

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Human sirtuins: Structures and flexibility

Cited by 36 publications

References 66 publications

The Roles of Sirtuin Family Proteins in Cancer Progression

The Roles of Sirtuin Family Proteins in Cancer Progression

Resveratrol Activated Sonic Hedgehog Signaling to Enhance Viability of NIH3T3 Cells in Vitro via Regulation of Sirt1

In Silico Study of Sirt1 Activators Using a Molecular Dynamic Approach

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