Structure of a Sir2 enzyme bound to an acetylated p53 peptide
Structure of a Sir2 enzyme bound to an acetylated p53 peptide
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DOI：
10.1016/s1097-2765(02)00628-7
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发表时间：
2002-09-01
期刊：
影响因子：
16
通讯作者：
Wolberger, C
中科院分区：
文献类型：
--
作者：
Avalos, JL;Celic, I;Wolberger, C
Sir 2蛋白是NAD（+）依赖的蛋白脱乙酰酶，在转录调控、DNA修复和寿命调节中起关键作用。古细菌Sir 2酶Sir 2-Af 2与乙酰化p53肽结合的结构表明，底物结合在酶的裂缝中，形成酶-底物0片层，在Sir 2-Af 2中具有两条侧翼链。乙酰赖氨酸插入到保守的疏水通道中，该疏水通道包含活性位点组氨酸。与其他结构的Sir 2酶的比较表明，脱辅基酶进行底物结合后的构象变化。基于Sir 2-Af 2底物复合物结构，在另一个A.闪电沉默调节蛋白，Sir 2-Af 1，增加了其对p53肽的亲和力。
Sir2 proteins are NAD(+)-dependent protein deacetylases that play key roles in transcriptional regulation, DNA repair, and life span regulation. The structure of an archaeal Sir2 enzyme, Sir2-Af2, bound to an acetylated p53 peptide reveals that the substrate binds in a cleft in the enzyme, forming an enzyme-substrate 0 sheet with two flanking strands in Sir2-Af2. The acetyllysine inserts into a conserved hydrophobic tunnel that contains the active site histidine. Comparison with other structures of Sir2 enzymes suggests that the apoenzyme undergoes a conformational change upon substrate binding. Based on the Sir2-Af2 substrate complex structure, mutations were made in the other A. fulgidus sirtuin, Sir2-Af1, that increased its affinity for the p53 peptide.