The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to type II ACPs
The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to type II ACPs
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DOI：
10.1039/b208941f
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发表时间：
2003-02-07
影响因子：
3.2
通讯作者：
Simpson, TJ
中科院分区：
文献类型：
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作者：
Reed, MAC;Schweizer, M;Simpson, TJ
虽然X射线和NMR结构现在可用于II型脂肪酸合酶（FAS）的大多数组分，但没有I型FAS结构域的结构。哺乳动物（大鼠）FAS的一个区域，包括假定的酰基载体蛋白（ACP），已被克隆和过表达。在这里，我们报告了多核、多维NMR研究，其显示该分离的ACP结构域包含四个α-螺旋（残基8 - 16 [1]; 41 - 51 [2]; 58 - 63 [3]和66 - 74 [4]）和来自II型FAS和聚酮酶（PKS）的ACP的总体全局折叠特征。双匕首结构化ACP结构域的总长度（67个残基）小于大肠杆菌FAS ACP（75个残基）、放线菌紫素PKS ACP（78个残基）和枯草芽孢杆菌FAS ACP（76个残基）的结构化区域。我们进一步表明，大鼠FAS ACP被公认为是一种有效的底物的酶，已知修改II型ACP，包括磷酸泛酰巯基乙胺和丙二酰转移酶，但不是由异源S。腔棘鱼最小聚酮合酶。
While X-ray and NMR structures are now available for most components of the Type II fatty acid synthase (FAS), there are no structures for Type I FAS domains. A region from the mammalian (rat) FAS, including the putative acyl carrier protein (ACP), has been cloned and over-expressed. Here we report multinuclear, multidimensional NMR studies which show that this isolated ACP domain contains four a-helices (residues 8-16 [1]; 41-51 [2]; 58-63 [3] and 66-74 [4]) and an overall global fold characteristic of ACPs from both Type II FAS and polyketide synthases (PKSs). double dagger The overall length of the structured ACP domain (67 residues) is smaller than the structured regions of the Eschericia coli FAS ACP (75 residues), the actinorhodin PKS ACP (78 residues) and the Bacillus subtilis FAS ACP (76 residues). We further show that the rat FAS ACP is recognised as an efficient substrate by enzymes known to modify Type II ACPs including phosphopantetheinyl and malonyl transferases, but not by the heterologous S. coelicolor minimal polyketide synthase.