Crystal structure and substrate specificity of the β-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus
Crystal structure and substrate specificity of the β-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus
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DOI：
10.1110/ps.051501605
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发表时间：
2005-08-01
期刊：
影响因子：
8
通讯作者：
Khandekar, SS
中科院分区：
文献类型：
--
作者：
Qiu, XY;Choudhry, AE;Khandekar, SS
β-酮酰基-ACP 合酶 III (FabH) 是细菌活力的必需酶，通过缩合丙二酰基-ACP 与乙酰辅酶 A 来催化脂肪酸延伸的启动。我们已经确定了金黄色葡萄球菌（一种革兰氏阳性人类病原体）的 FabH 晶体结构，分辨率为 2 A。尽管金黄色葡萄球菌 FabH 的整体结构与大肠杆菌 FabH 相似，但金黄色葡萄球菌 FabH 中的引物结合袋明显大于大肠杆菌 FabH 中的引物结合袋。与动力学参数一致的结构差异为观察到的大肠杆菌和金黄色葡萄球菌 FabH 的不同底物特异性提供了解释。金黄色葡萄球菌FabH与各种酰基-CoA引物的活性排序如下：异丁酰->己酰->丁酰->异戊酰乙酰-CoA。晶体结构的可用性可能有助于设计有效的、选择性的金黄色葡萄球菌 FabH 抑制剂。
beta-Ketoacyl-ACP synthase III (FabH), an essential enzyme for bacterial viability, catalyzes the initiation of fatty acid elongation by condensing malonyl-ACP with acetyl-CoA. We have determined the crystal structure of FabH from Staphylococcus aureus, a Gram-positive human pathogen, to 2 A resolution. Although the overall structure of S. aureus FabH is similar to that of Escherichia coli FabH, the primer binding pocket in S. aureus FabH is significantly larger than that present in E. coli FabH. The structural differences, which agree with kinetic parameters, provide explanation for the observed varying substrate specificity for E. coli and S. aureus FabH. The rank order of activity of S. aureus FabH with various acyl-CoA primers was as follows: isobutyryl- > hexanoyl- > butyryl- > isovalerylacetyl-CoA. The availability of crystal structure may aid in designing potent, selective inhibitors of S. aureus FabH.