The 2.7-Å crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase
The 2.7-Å crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase
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DOI：
10.1073/pnas.0601924103
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发表时间：
2006-07-25
影响因子：
11.1
通讯作者：
Khosla, Chaitan
中科院分区：
文献类型：
--
作者：
Tang, Yinyan;Kim, Chu-Young;Khosla, Chaitan
6-脱氧赤藓内酯B合成酶模数为5的194 kDa片段的X射线晶体结构已在2.7埃分辨率下得到解析。同源二聚体蛋白的每个亚基都包含一个全长酮合成酶(KS)和酰基转移酶(AT)结构域以及三个侧翼的“连接子”。连接子在结构上定义良好，经常通过多个高度保守的残基对亚基间或结构域间的相互作用做出广泛贡献。晶体结构还表明，KS结构域的活性中心残基Cys-199与AT结构域的活性中心残基Ser-642相差约80埃。这一距离太大了，不能简单地通过替换模块5中酰基载体蛋白结构域的静态锚定的、完全延伸的磷酸丙氨酸臂来覆盖。因此，大量的结构域重组似乎是酰基载体蛋白与这个原型聚酮合成酶模块的AT和KS结构域连续相互作用所必需的。2.7埃的KS-AT结构与最近报道的较低分辨率、4.5埃的脂肪酸合成酶结构模型完全一致，并强调了聚酮合成酶和脂肪酸合成酶在生化和结构上的相似性。
The x-ray crystal structure of a 194-kDa fragment from module 5 of the 6-deoxyerythronolide B synthase has been solved at 2.7 angstrom resolution. Each subunit of the homodimeric protein contains a full-length ketosynthase (KS) and acyl transferase (AT) domain as well as three flanking "linkers." The linkers are structurally well defined and contribute extensively to intersubunit or interdomain interactions, frequently by means of multiple highly conserved residues. The crystal structure also reveals that the active site residue Cys-199 of the KS domain is separated from the active site residue Ser-642 of the AT domain by approximate to 80 angstrom. This distance is too large to be covered simply by alternative positioning of a statically anchored, fully extended phosphopantetheine arm of the acyl carrier protein domain from module 5. Thus, substantial domain reorganization appears necessary for the acyl carrier protein to interact successively with both the AT and the KS domains of this prototypical polyketide synthase module. The 2.7-angstrom KS-AT structure is fully consistent with a recently reported lower resolution, 4.5-angstrom model of fatty acid synthase stucture, and emphasizes the close biochemical and structural similarity between polyketide synthase and fatty acid synthase enzymology.