Crystal Structures of Enoyl-ACP Reductases I (FabI) and III (FabL) from B. subtilis
Crystal Structures of Enoyl-ACP Reductases I (FabI) and III (FabL) from B. subtilis
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DOI：
10.1016/j.jmb.2010.12.003
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发表时间：
2011-02-25
影响因子：
5.6
通讯作者：
Kim, Eunice EunKyeong
中科院分区：
文献类型：
--
作者：
Kim, Kook-Han;Ha, Byung Hak;Kim, Eunice EunKyeong
烯酰基-[酰基载体蛋白] (ACP) 还原酶 (ENR) 是 II 型脂肪酸合成中的关键酶，可催化每个延伸周期的最后一步。因此，它被认为是抗生素的靶点。然而，最近的研究表明，一些病原体具有不止一种 ENR；特别地，枯草芽孢杆菌具有两个ENR：FabI和FabL。 BsFaBI 和 BsFabL 三元复合物的晶体结构被发现为同源四聚体，尽管序列同一性仅为 24%，但显示出相同的整体结构。 FabL 中 Tyr-(Xaa)(6)-Lys 催化二元体的位置与 FabI 几乎相同，但详细的结构分析表明 FabL 与 FabG 和 SDR（短链醇脱氢酶/还原酶）家族的其他成员有更多的结构相似性。 apo FabL 结构在辅因子和底物结合区域显示出显着不同的构象，这导致完全不同的四聚体排列，反映了在辅因子和底物/抑制剂不存在的情况下这些区域的灵活性。 (C) 2010 Elsevier Ltd. 保留所有权利。
Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II fatty acid synthesis that catalyzes the last step in each elongation cycle. Therefore, it has been considered as a target for antibiotics. However, recent studies indicate that some pathogens have more than one ENR; in particular, Bacillus subtilis has two ENRs, FabI and FabL. The crystal structures of the ternary complexes of BsFaBI and BsFabL are found as a homotetramer showing the same overall structure despite a sequence identity of only 24%. The positions of the catalytic dyad of Tyr-(Xaa)(6)-Lys in FabL are almost identical to that of FabI, but a detailed structural analysis shows that FabL shares more structural similarities with FabG and other members of the SDR (short-chain alcohol dehydrogenase/reductase) family. The apo FabL structure shows significantly different conformations at the cofactor and the substrate-binding regions, and this resulted in a totally different tetrameric arrangement reflecting the flexibility of these regions in the absence of the cofactor and substrate/inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.