PDF(Pubmed)
Abstract：
The initial adoption of penicillin as an antibiotic marked the start of exploring other compounds essential for pharmaceuticals, yet resistance to penicillins and their side effects has compromised their efficacy. The N-terminal nucleophile (Ntn) amide-hydrolases S45 family plays a key role in catalyzing amide bond hydrolysis in various compounds, including antibiotics like penicillin and cephalosporin. This study comprehensively analyzes the structural and functional traits of the bacterial N-terminal nucleophile (Ntn) amide-hydrolases S45 family, covering penicillin G acylases, cephalosporin acylases, and D-succinylase. Utilizing structural bioinformatics tools and sequence analysis, the investigation delineates structurally conserved regions (SCRs) and substrate binding site variations among these enzymes. Notably, sixteen SCRs crucial for substrate interaction are identified solely through sequence analysis, emphasizing the significance of sequence data in characterizing functionally relevant regions. These findings introduce a novel approach for identifying targets to enhance the biocatalytic properties of N-terminal nucleophile (Ntn) amide-hydrolases, while facilitating the development of more accurate three-dimensional models, particularly for enzymes lacking structural data. Overall, this research advances our understanding of structure-function relationships in bacterial N-terminal nucleophile (Ntn) amide-hydrolases, providing insights into strategies for optimizing their enzymatic capabilities.
摘要：
青霉素作为抗生素的最初采用标志着探索药物必需的其他化合物的开始，然而，对青霉素的抗性及其副作用已经损害了它们的功效。N末端亲核试剂（Ntn）酰胺水解酶S45家族在催化各种化合物的酰胺键水解中起关键作用，包括抗生素如青霉素和头孢菌素.本研究全面分析了细菌N-末端亲核试剂(Ntn)酰胺水解酶S45家族的结构和功能性状,涵盖青霉素G酰基酶，头孢菌素酰基转移酶，和D-琥珀酰基转移酶.利用结构生物信息学工具和序列分析，该研究描述了这些酶之间的结构保守区域（SCR）和底物结合位点变异。值得注意的是,16个对底物相互作用至关重要的SCR仅通过序列分析鉴定，强调序列数据在表征功能相关区域中的重要性。这些发现为识别靶标以增强N末端亲核试剂（Ntn）酰胺水解酶的生物催化特性引入了一种新方法，在促进开发更精确的三维模型的同时，特别是对于缺乏结构数据的酶。总的来说,这项研究促进了我们对细菌N末端亲核（Ntn）酰胺水解酶中结构-功能关系的理解，提供对优化其酶能力的策略的见解。
