Crystal structure of long-chain alkane monooxygenase (LadA) in complex with coenzyme FMN: Unveiling the long-chain alkane hydroxylase
Crystal structure of long-chain alkane monooxygenase (LadA) in complex with coenzyme FMN: Unveiling the long-chain alkane hydroxylase
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DOI：
10.1016/j.jmb.2007.11.069
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发表时间：
2008-02-15
影响因子：
5.6
通讯作者：
Rao, Zihe
中科院分区：
文献类型：
--
作者：
Li, Liu;Liu, Xueqian;Rao, Zihe
LadA是一种长链烷烃单加氧酶，在嗜热芽孢杆菌Geobacillus thermorecyclificans NG 80 -2中利用末端氧化途径将长链烷烃（最多至少C-36）转化为相应的伯醇。在这里，我们报告的第一个结构的长链烷烃羟化酶，LadA，和它的复杂的黄素单核苷酸（FMN）辅酶。LadA通过令人惊讶的结构关系被表征为细菌荧光素酶家族的SsuD亚家族的新成员。LadA：FMN二元复合物结构和LadA：FMN：烷烃模型揭示了具有双重作用的疏水空腔：提供用于催化的氢键供体（His 138），并创建无溶剂环境，以稳定C4 a-氢过氧黄素中间体。因此，LadA应该通过公认的黄素蛋白单加氧酶机制催化长链烷烃的转化。这一发现表明，LadA催化降解长链烷烃的能力是由长链烷烃底物的结合模式决定的。LadA的结构为探索和改变LadA的底物结合位点提供了一个合理的视角，在石油勘探和环境石油污染治理等领域具有潜在的生物技术应用。(C)2007爱思唯尔有限公司版权所有。
LadA, a long-chain alkane monooxygenase, utilizes a terminal oxidation pathway for the conversion of long-chain alkanes (up to at least C-36) to corresponding primary alcohols in thermophilic bacillus Geobacillus thermodenitrificans NG80-2. Here, we report the first structure of the long-chain alkane hydroxylase, LadA, and its complex with the flavin mononucleotide (FMN) coenzyme. LadA is characterized as a new member of the SsuD subfamily of the bacterial luciferase family via a surprising structural relationship. The LadA:FMN binary complex structure and a LadA:FMN:alkane model reveal a hydrophobic cavity that has dual roles: to provide a hydrogen-bond donor (His138) for catalysis and to create a solvent-free environment in which to stabilize the C4a-hydroperoxyflavin intermediate. Consequently, LadA should catalyze the conversion of long-chain alkanes via the acknowledged flavoprotein monooxygenase mechanism. This finding suggests that the ability of LadA to catalyze the degradation of long-chain alkanes is determined by the binding mode of the long-chain alkane substrates. The LadA structure opens a rational perspective to explore and alter the substrate binding site of LadA, with potential biotechnological applications in areas such as petroleum exploration and treatment of environmental oil pollution. (C) 2007 Elsevier Ltd. All rights reserved.