5OJN

Sirtuin 4 from Xenopus tropicalis in complex with thioacetyl-ADP-ribose

Summary for 5OJN

• Entry DOI: 10.2210/pdb5ojn/pdb
• Related: 5OJ7 5OJO
• Descriptor: NAD-dependent protein deacylase, ZINC ION, thioacetyl-ADP-ribose, ... (4 entities in total)
• Functional Keywords: sirtuin, sirt4, deacylase, mitochondria, signaling protein
• Biological source: Xenopus tropicalis (Western clawed frog)
• Cellular location: Mitochondrion matrix : Q28CB4
• Total number of polymer chains: 1
• Total formula weight: 32783.23

Authors

Pannek, M.,Steegborn, C. (deposition date: 2017-07-22, release date: 2017-11-29, Last modification date: 2024-10-16)

Primary citation

Pannek, M.,Simic, Z.,Fuszard, M.,Meleshin, M.,Rotili, D.,Mai, A.,Schutkowski, M.,Steegborn, C.
Crystal structures of the mitochondrial deacylase Sirtuin 4 reveal isoform-specific acyl recognition and regulation features.
Nat Commun, 8:1513-1513, 2017

PubMed Abstract: Sirtuins are evolutionary conserved NAD-dependent protein lysine deacylases. The seven human isoforms, Sirt1-7, regulate metabolism and stress responses and are considered therapeutic targets for aging-related diseases. Sirt4 locates to mitochondria and regulates fatty acid metabolism and apoptosis. In contrast to the mitochondrial deacetylase Sirt3 and desuccinylase Sirt5, no prominent deacylase activity and structural information are available for Sirt4. Here we describe acyl substrates and crystal structures for Sirt4. The enzyme shows isoform-specific acyl selectivity, with significant activity against hydroxymethylglutarylation. Crystal structures of Sirt4 from Xenopus tropicalis reveal a particular acyl binding site with an additional access channel, rationalizing its activities. The structures further identify a conserved, isoform-specific Sirt4 loop that folds into the active site to potentially regulate catalysis. Using these results, we further establish efficient Sirt4 activity assays, an unusual Sirt4 regulation by NADH, and Sirt4 effects of pharmacological modulators.

PubMed: 29138502
DOI: 10.1038/s41467-017-01701-2

Experimental method

X-RAY DIFFRACTION (1.8 Å)