5OJ7

Sirtuin 4 orthologue from Xenopus Tropicalis in complex with ADP-ribose

5OJ7 の概要

• エントリーDOI: 10.2210/pdb5oj7/pdb
• 関連するPDBエントリー: 5OJN 5OJO
• 分子名称: NAD-dependent protein deacylase, [(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE, ZINC ION, ... (6 entities in total)
• 機能のキーワード: sirt4 deacylase posttranslational modification, hydrolase
• 由来する生物種: Xenopus tropicalis (Western clawed frog)
• 細胞内の位置: Mitochondrion matrix : Q28CB4
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33065.49

構造登録者

Pannek, M.,Steegborn, C. (登録日: 2017-07-20, 公開日: 2017-11-29, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.58 Å)