Crystal structure of yeast acetyl-coenzyme A synthetase in complex with AMP
Crystal structure of yeast acetyl-coenzyme A synthetase in complex with AMP
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DOI：
10.1021/bi035911a
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发表时间：
2004-02-17
期刊：
影响因子：
2.9
通讯作者：
Tong, L
中科院分区：
文献类型：
--
作者：
Jogl, G;Tong, L
乙酰辅酶A合成酶（ACS）属于AMP形成酶家族，该家族还包括酰基辅酶A合成酶、萤火虫荧光素酶和非核糖体肽合成酶。ACS催化乙酸盐活化为乙酰辅酶A的两步反应：由乙酸盐和ATP形成乙酰AMP中间体，并将乙酰基转移至辅酶A。在哺乳动物中，乙酰辅酶A产物用于长链脂肪酸的生物合成以及能量生产。我们已经确定了晶体结构的酵母ACS的二元复合物与AMP在2.3埃的分辨率。该结构包含一个大的N-末端结构域和一个小的C-末端结构域。AMP结合在两个结构域之间的界面处。这种结构代表了ACS酶的一种新构象，它可能能够催化反应的第一步。对该步骤至关重要的Lys残基位于活性位点。在小畴内旋转140度，才能结合CoA并催化第二步反应。与单体细菌酶相反，酵母ACS是稳定的三聚体。
Acetyl-coenzyme A synthetase (ACS) belongs to the family of AMP-forming enzymes that also includes acyl-CoA synthetases, firefly luciferase, and nonribosomal peptide synthetases. ACS catalyzes the two-step activation of acetate to acetyl-CoA: formation of an acetyl-AMP intermediate from acetate and ATP and the transfer of the acetyl group to CoA. In mammals, the acetyl-CoA product is used for biosynthesis of long chain fatty acids as well as energy production. We have determined the crystal structure of yeast ACS in a binary complex with AMP at 2.3 Angstrom resolution. The structure contains a large, N-terminal domain and a small, C-terminal domain. AMP is bound at the interface between the two domains. This structure represents a new conformation for the ACS enzyme, which may be competent for catalyzing the first step of the reaction. A Lys residue that is critical for this step is located in the active site. A rotation of 140degrees in the small domain is needed for the binding of CoA and the catalysis of the second step. In contrast to the monomeric bacterial enzyme, yeast ACS is a stable trimer.