Crystal structure of the histone acetyltransferase Hpa2:: A tetrameric member of the Gcn5-related N-acetyltransferase superfamily
Crystal structure of the histone acetyltransferase Hpa2:: A tetrameric member of the Gcn5-related N-acetyltransferase superfamily
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DOI：
10.1006/jmbi.1999.3338
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发表时间：
1999-12-17
影响因子：
5.6
通讯作者：
Ramakrishnan, V
中科院分区：
文献类型：
--
作者：
Angus-Hill, ML;Dutnall, RN;Ramakrishnan, V
我们报告的晶体结构的酵母蛋白Hpa 2在复杂的乙酰辅酶A（AcCoA）在2.4埃分辨率和没有辅因子在2.9埃分辨率。Hpa 2是Gcn 5相关的N-乙酰转移酶（GNAT）超家族的成员，GNAT超家族是具有不同底物的酶家族，包括组蛋白、其他蛋白质、芳基烷基胺和氨基糖苷类。在体外，Hpa 2能够乙酰化组蛋白H3和H4的特异性赖氨酸残基，优选组蛋白H3的Lys 14。Hpa 2在溶液中形成稳定的二聚体，并在结合AcCoA时形成四聚体。晶体结构表明，Hpa 2四聚体是稳定的结合乙酰辅酶A分子的腺嘌呤部分之间的碱基对相互作用。这些碱基对代表了稳定寡聚蛋白质结构的新方法。Hpa 2与其他GNAT超家族成员的结构的比较说明了GNAT家族的催化结构域的显著保守的折叠，即使该家族的成员共享低水平的序列同源性。这种比较使我们能够更好地定义GNAT家族的四个序列基序的边界，包括一个基序，这是不能单独通过序列比较在组蛋白乙酰转移酶辨别。我们讨论了Hpa 2结构的GNAT酶的催化机制的影响和多组蛋白尾部修饰的四聚体Hpa 2结构的机会。(C)北京：科学出版社.
We report the crystal structure of the yeast protein Hpa2 in complex with acetyl coenzyme A (AcCoA) at 2.4 Angstrom resolution and without cofactor at 2.9 Angstrom resolution. Hpa2 is a member of the Gcn5-related N-acetyltransferase (GNAT) superfamily, a family of enzymes with diverse substrates including histones, other proteins, arylalkylamines and aminoglycosides. In vitro, Hpa2 is able to acetylate specific lysine residues of histones H3 and H4 with a preference for Lys14 of histone H3. Hpa2 forms a stable dimer in solution and forms a tetramer upon binding AcCoA. The crystal structure reveals that the Hpa2 tetramer is stabilized by base-pair interactions between the adenine moieties of the bound AcCoA molecules. These base-pairs represent a novel method of stabilizing an oligomeric protein structure. Comparison of the structure of Hpa2 with those of other GNAT superfamily members illustrates a remarkably conserved fold of the catalytic domain of the GNAT family even though members of this family share low levels of sequence homology. This comparison has allowed us to better define the borders of the four sequence motifs that characterize the GNAT family, including a motif that is not discernable in histone acetyltransferases by sequence comparison alone. We discuss implications of the Hpa2 structure for the catalytic mechanism of the GNAT enzymes and the opportunity for multiple histone tail modification created by the tetrameric Hpa2 structure. (C) 1999 Academic Press.