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首页> 外文期刊>Applied Microbiology >An α/β-Hydrolase Fold Subfamily Comprising Pseudomonas Quinolone Signal-Cleaving Dioxygenases
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An α/β-Hydrolase Fold Subfamily Comprising Pseudomonas Quinolone Signal-Cleaving Dioxygenases

机译：α/β-水解酶折叠亚类，包含喹诺酮类喹啉纤维裂解二恶英酶

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The quinolone ring is a common core structure of natural products exhibiting antimicrobial, cytotoxic, and signaling activities. A prominent example is the Pseudomonas quinolone signal (PQS), a quorum-sensing signal molecule involved in the regulation of virulence of Pseudomonas aeruginosa . The key reaction to quinolone inactivation and biodegradation is the cleavage of the 3-hydroxy-4(1 H )-quinolone ring, catalyzed by dioxygenases (HQDs), which are members of the α/β-hydrolase fold superfamily. The α/β-hydrolase fold core domain consists of a β-sheet surrounded by α-helices, with an active site usually containing a catalytic triad comprising a nucleophilic residue, an acidic residue, and a histidine. The nucleophile is located at the tip of a sharp turn, called the “nucleophilic elbow.” In this work, we developed a search workflow for the identification of HQD proteins from databases. Search and validation criteria include an [H-x(2)-W] motif at the nucleophilic elbow, an [HFP-x(4)-P] motif comprising the catalytic histidine, the presence of a helical cap domain, the positioning of the triad’s acidic residue at the end of β-strand 6, and a set of conserved hydrophobic residues contributing to the substrate cavity. The 161 candidate proteins identified from the UniProtKB database originate from environmental and plant-associated microorganisms from all domains of life. Verification and characterization of HQD activity of 9 new candidate proteins confirmed the reliability of the search strategy and suggested residues correlating with distinct substrate preferences. Among the new HQDs, PQS dioxygenases from Nocardia farcinica , N. cyriacigeorgica , and Streptomyces bingchenggensis likely are part of a catabolic pathway for alkylquinolone utilization.IMPORTANCE Functional annotation of protein sequences is a major requirement for the investigation of metabolic pathways and the identification of sought-after biocatalysts. To identify heterocyclic ring-cleaving dioxygenases within the huge superfamily of α/β-hydrolase fold proteins, we defined search and validation criteria for the primarily motif-based identification of 3-hydroxy-4(1 H )-quinolone 2,4-dioxygenases (HQD). HQDs are key enzymes for the inactivation of metabolites, which can have signaling, antimicrobial, or cytotoxic functions. The HQD candidates detected in this study occur particularly in environmental and plant-associated microorganisms. Because HQDs active toward the Pseudomonas quinolone signal (PQS) likely contribute to interactions within microbial communities and modulate the virulence of Pseudomonas aeruginosa , we analyzed the catalytic properties of a PQS-cleaving subset of HQDs and specified characteristics to identify PQS-cleaving dioxygenases within the HQD family.
机译：喹诺酮环是具有抗菌，细胞毒性和信号活动的天然产品的常见核心结构。突出的例子是假单胞菌喹诺酮信号（PQS），一种涉及假鼠铜绿假单胞菌毒力调节的仲裁传感信号分子。对喹诺酮失活和生物降解的关键反应是通过二氧化基酶（HQDS）催化的3-羟基-4（1H）-quinolone环的切割，其是α/β-水解酶折叠超家族的成员。 α/β-水解酶折叠芯结构域由α-螺旋包围的β-薄片组成，活性位点通常含有催化三合会，其包含亲核残余物，酸性残基和组氨酸。亲核官位于尖端的尖端，称为“亲核肘关节”。在这项工作中，我们开发了一个搜索工作流程，用于从数据库中识别HQD蛋白。搜索和验证标准包括在亲核肘部的[HX（2）-W]图案，包含催化组氨酸的[HFP-X（4）-P]基序，螺旋帽结构域的存在，TRIAD的定位β-链6的末端的酸性残余物，以及一组助长的疏水性残基，有助于基板腔。从UniProtkB数据库中鉴定的161个候选蛋白质来自生命域的环境和植物相关的微生物。 9个新候选蛋白的HQD活性的验证和表征证实了搜索策略的可靠性和与不同的基材偏好相关的建议残留物。来自Nocardia Farcinica，N.CyriaciGeorgica的PQS DiOxygenase和Streptomyces Bingchengensis可能是烷基喹诺酮类利用的分解途径的一部分。分解蛋白质序列的功能注释是对代谢途径调查的主要要求和寻求的鉴定 - 生物催化剂。为了鉴定α/β-水解酶折叠蛋白的巨大超家族内的杂环环裂解二恶英酶，我们定义了用于基于基于基于基于基于基于基于基于基于基于主题的3-羟基-4（1 h）-quinolone 2,4-二氧基酶的搜索和验证标准（HQD）。 HQDS是代谢物失活的关键酶，其可以具有信号，抗微生物或细胞毒性功能。在本研究中检测到的HQD候选者特别是在环境和植物相关的微生物中。由于HQDS朝向假单胞菌的喹啉信号（PQS）可能有助于微生物群落中的相互作用并调节假单胞菌铜绿假单胞菌的毒力，我们分析了PQS切割HQDS和特定特征的催化性质，以鉴定在其中的PQS切割的二氧化基酶HQD家族。

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