Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase
Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase
复制标题
DOI：
10.1016/s0969-2126(03)00004-2
复制
发表时间：
2003-02-01
期刊：
影响因子：
5.7
通讯作者：
Stroud, RM
中科院分区：
文献类型：
--
作者：
Keatinge-Clay, AT;Shelat, AA;Stroud, RM
丙二酰辅酶A：ACP转酰酶（MAT）是天蓝色链霉菌的fabD基因产物3（2），参与脂肪酸和聚酮化合物合成途径，将丙二酰辅酶A链生长中用作延伸单元的丙二酰基团转移至途径特异性酰基载体蛋白（ACP）。在这里，2.0埃结构揭示了与乙酸酯结合的不变精氨酸，其模拟丙二酰羧酸酯并帮助限定延伸单元结合位点。只有当含氧阴离子空穴通过底物结合形成时，才可能发生催化作用，从而阻止酰基酶中间体的水解。与放线菌紫素ACP的大分子对接模拟表明，大多数的ACP对接表面是由一个螺旋皮瓣形成的。这些结果将有助于工程聚酮酶（PKS），产生新的聚酮。
Malonyl-CoA:ACP transacylase (MAT), the fabD gene product of Streptomyces coelicolor 3(2), participates in both fatty acid and polyketide synthesis pathways, transferring malonyl groups that are used as extender units in chain growth from malonyl-CoA to pathway-specific acyl carrier proteins (ACPs). Here, the 2.0 Angstrom structure reveals an invariant arginine bound to an acetate that mimics the malonyl carboxylate and helps define the extender unit binding site. Catalysis may only occur when the oxyanion hole is formed through substrate binding, preventing hydrolysis of the acylenzyme intermediate. Macromolecular docking simulations with actinorhodin ACP suggest that the majority of the ACP docking surface is formed by a helical flap. These results should help to engineer polyketide synthases (PKSs) that produce novel polyketides.