High-resolution structures of AidH complexes provide insights into a novel catalytic mechanism for N-acyl homoserine lactonase
High-resolution structures of AidH complexes provide insights into a novel catalytic mechanism for N-acyl homoserine lactonase
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AidH 复合物的高分辨率结构为 N-酰基高丝氨酸内酯酶的新型催化机制提供了见解
DOI：
10.1107/s0907444912042369
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发表时间：
2013-01-01
影响因子：
2.2
通讯作者：
Liang, Dong-cai
中科院分区：
文献类型：
--
作者：
Gao, Ang;Mei, Gui-ying;Liang, Dong-cai
许多感染人类、动物和植物的致病菌依赖于群体感应(QS)系统来产生毒力因子。N-酰基高丝氨酸内酯(AHLS)是QS中最具特征性的细胞间通讯信号。AHL的浓度对病原菌的毒力基因表达和基本生物学功能起着关键的调节作用。N-酰基高丝氨酸内酰胺酶(AHL-lactonase)通过降解AHLS，在降低致病性方面具有重要作用。本文报道了Ochrobactrum sp.的AHL-内酯酶的结构。本文报道了N-己酰高丝氨酸内酯、N-己酰高丝氨酸和N-丁酰高丝氨酸的配合物(AIDH)。高分辨率结构和生化分析揭示了AHL降解的令人信服的细节。与其他具有双Lewis酸催化机制的AHL-内酯酶不同，该酶的活性中心不结合金属离子。AIDH在核心域和CAP结构域之间包含底物结合隧道。隧道入口的构象随AHL酰链长度的不同而不同，这有助于AHL分子在活性中心的结合混杂。支持AIDH是一种广谱AHL-内酰胺酶的生化结果。综上所述，本研究结果揭示了金属依赖的AHL-内酯酶的催化机理，该酶是典型的酸碱共价催化。
Many pathogenic bacteria that infect humans, animals and plants rely on a quorum-sensing (QS) system to produce virulence factors. N-Acyl homoserine lactones (AHLs) are the best-characterized cell-cell communication signals in QS. The concentration of AHL plays a key role in regulating the virulence-gene expression and essential biological functions of pathogenic bacteria. N-Acyl homoserine lactonases (AHL-lactonases) have important functions in decreasing pathogenicity by degrading AHLs. Here, structures of the AHL-lactonase from Ochrobactrum sp. (AidH) in complex with N-hexanoyl homoserine lactone, N-hexanoyl homoserine and N-butanoyl homoserine are reported. The high-resolution structures together with biochemical analyses reveal convincing details of AHL degradation. No metal ion is bound in the active site, which is different from other AHL-lactonases, which have a dual Lewis acid catalysis mechanism. AidH contains a substrate-binding tunnel between the core domain and the cap domain. The conformation of the tunnel entrance varies with the AHL acyl-chain length, which contributes to the binding promiscuity of AHL molecules in the active site. It also supports the biochemical result that AidH is a broad catalytic spectrum AHL-lactonase. Taken together, the present results reveal the catalytic mechanism of the metalin-dependent AHL-lactonase, which is a typical acid-base covalent catalysis.