Structure of the histone deacetylase SIRT2
Structure of the histone deacetylase SIRT2
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DOI：
10.1038/89668
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发表时间：
2001-07-01
期刊：
影响因子：
--
通讯作者：
Pavletich, NP
中科院分区：
文献类型：
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作者：
Finnin, MS;Donigian, JR;Pavletich, NP
Sir2 是一种 NAD 依赖性组蛋白脱乙酰酶，介导交配型位点、端粒和核糖体基因簇的转录沉默，在酵母和秀丽隐杆线虫的寿命决定中具有关键作用。人 SIRT2（酵母 Sir2 的同源物）的 323 个氨基酸催化核心的 1.7 埃晶体结构揭示了 NAD 结合结构域（罗斯曼折叠的变体）以及由螺旋模块和锌结合模块组成的较小结构域。两个结构域界面处的保守大凹槽是基于诱变的可能的催化位点，与该大凹槽相交，存在由螺旋模块形成的口袋。该口袋排列有五个 Sir2 类别中每一个类别中保守的疏水残基，表明它是类别特异性蛋白质结合位点。
Sir2 is an NAD-dependent histone deacetylase that mediates transcriptional silencing at mating-type loci, telomeres and ribosomal gene dusters, and has a critical role in the determination of life span in yeast and Caenorhabditis elegans. The 1.7 Angstrom crystal structure of the 323 amino acid catalytic core of human SIRT2, a homolog of yeast Sir2, reveals an NAD-binding domain, which is a variant of the Rossmann fold, and a smaller domain composed of a helical module and a zinc-binding module. A conserved large groove at the interface of the two domains is the likely site of catalysis based on mutagenesis, intersecting this large groove, there is a pocket formed by the helical module. The pocket is lined with hydrophobic residues conserved within each of the five Sir2 classes, suggesting that it is a class-specific protein-binding site.