7BOT

Human SIRT2 in complex with myristoyl thiourea inhibitor, No.23

Summary for 7BOT

• Entry DOI: 10.2210/pdb7bot/pdb
• Related PRD ID: PRD_002360
• Descriptor: NAD-dependent protein deacetylase sirtuin-2, myristoyl thiourea inhibitor, No.23, ZINC ION, ... (5 entities in total)
• Functional Keywords: nad-dependent deacetylase, deacylase, inhibitor complex, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 34017.69

Authors

Kudo, N.,Olsen, C.A.,Minoru, Y. (deposition date: 2020-03-19, release date: 2021-03-24, Last modification date: 2023-11-29)

Primary citation

Nielsen, A.L.,Rajabi, N.,Kudo, N.,Lundo, K.,Moreno-Yruela, C.,Baek, M.,Fontenas, M.,Lucidi, A.,Madsen, A.S.,Yoshida, M.,Olsen, C.A.
Mechanism-based inhibitors of SIRT2: structure-activity relationship, X-ray structures, target engagement, regulation of alpha-tubulin acetylation and inhibition of breast cancer cell migration.
Rsc Chem Biol, 2:612-626, 2021

PubMed Abstract: Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. It affects diverse biological functions in the cell and has been considered a drug target in relation to both neurodegenerative diseases and cancer. Therefore, access to well-characterized and robust tool compounds is essential for the continued investigation of the complex functions of this enzyme. Here, we report a collection of chemical probes that are potent, selective, stable in serum, water-soluble, and inhibit SIRT2-mediated deacetylation and demyristoylation in cells. Compared to the current landscape of SIRT2 inhibitors, this is a unique ensemble of features built into a single compound. We expect the developed chemotypes to find broad application in the interrogation of SIRT2 functions in both healthy and diseased cells, and to provide a foundation for the development of future therapeutics.

PubMed: 34458803
DOI: 10.1039/d0cb00036a

Experimental method

X-RAY DIFFRACTION (1.7 Å)