4G1C

Human SIRT5 bound to Succ-IDH2 and Carba-NAD

4G1C の概要

• エントリーDOI: 10.2210/pdb4g1c/pdb
• 関連するPDBエントリー: 4FVT
• 分子名称: NAD-dependent protein deacylase sirtuin-5, mitochondrial, Succinylated IDH2 peptide, ZINC ION, ... (5 entities in total)
• 機能のキーワード: sirtuin, succinylated peptide, carbanad, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Mitochondrion matrix. Isoform 1: Cytoplasm. Isoform 2: Mitochondrion: Q9NXA8
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 60130.99

構造登録者

Dai, H. (登録日: 2012-07-10, 公開日: 2012-08-15, 最終更新日: 2025-03-26)

主引用文献

Szczepankiewicz, B.G.,Dai, H.,Koppetsch, K.J.,Qian, D.,Jiang, F.,Mao, C.,Perni, R.B.
Synthesis of Carba-NAD and the Structures of Its Ternary Complexes with SIRT3 and SIRT5.
J.Org.Chem., 77:7319-7329, 2012

PubMed Abstract: Carba-NAD is a synthetic compound identical to NAD except for one substitution, where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is replaced with a methylene group. Because it is inert in nicotinamide displacement reactions, carba-NAD is an unreactive substrate analogue for NAD-consuming enzymes. SIRT3 and SIRT5 are NAD-consuming enzymes that are potential therapeutic targets for the treatment of metabolic diseases and cancers. We report an improved carba-NAD synthesis, including a pyrophosphate coupling method that proceeds in approximately 60% yield. We also disclose the X-ray crystal structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide substrate and carba-NAD. These X-ray crystal structures provide critical snapshots of the mechanism by which human sirtuins function as protein deacylation catalysts.

PubMed: 22849721
DOI: 10.1021/jo301067e

実験手法

X-RAY DIFFRACTION (1.944 Å)