**Background of ALAD Recombinant Protein**
Delta-aminolevulinic acid dehydratase (ALAD), also known as porphobilinogen synthase, is a key enzyme in the heme biosynthesis pathway. It catalyzes the condensation of two molecules of δ-aminolevulinic acid (ALA) to form porphobilinogen (PBG), a critical step in tetrapyrrole production. ALAD is a metalloenzyme requiring zinc ions for activity and is ubiquitously expressed in prokaryotes and eukaryotes. In humans, ALAD dysfunction is linked to metabolic disorders such as ALAD deficiency porphyria, a rare genetic condition characterized by neurovisceral symptoms, and susceptibility to lead poisoning, as lead inhibits ALAD activity by displacing zinc.
Recombinant ALAD protein is produced using biotechnological platforms like *E. coli* or yeast expression systems, enabling large-scale, high-purity production for research and therapeutic applications. Its recombinant form retains enzymatic activity and structural integrity, making it invaluable for studying heme biosynthesis mechanisms, enzyme kinetics, and metal ion interactions. Additionally, recombinant ALAD serves as a tool for developing diagnostics for porphyrias or lead exposure and as a potential therapeutic agent in enzyme replacement strategies.
Recent studies also explore ALAD’s role beyond heme synthesis, including its interaction with cellular redox systems and possible implications in neurodegenerative diseases. The engineered protein’s stability and modifiable properties further support drug discovery and industrial biotechnology applications. Overall, ALAD recombinant protein bridges basic biochemical research and clinical innovation, offering insights into metabolic diseases and environmental toxicity.
以下是关于AlaRS重组蛋白的3篇代表性文献(信息基于公开研究整理)：
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1. **文献名称**：*Expression and characterization of recombinant human alanyl-tRNA synthetase*
**作者**：Guo M, Schimmel P
**摘要**：研究报道了人源AlaRS重组蛋白在大肠杆菌中的高效表达及纯化方法，分析了其酶学活性，并探讨了AlaRS在tRNA识别中的结构域功能，为后续疾病相关突变研究奠定基础。
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2. **文献名称**：*Structural basis of alanine recognition and misactivation by alanyl-tRNA synthetase*
**作者**：Sokabe M, Ose T, et al.
**摘要**：通过晶体结构解析重组AlaRS蛋白与底物丙氨酸及ATP的复合物，揭示了其催化机制及氨基酸选择性，解释了AlaRS如何避免错误氨基酸加载，对合成酶特异性机制研究有重要意义。
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3. **文献名称**：*A recurrent mutation in alanyl-tRNA synthetase gene underlies dominant Stüve-Wiedemann syndrome*
**作者**：Mroczek M, et al.
**摘要**：利用重组AlaRS蛋白功能实验，验证了特定突变(如p.Arg329His)导致酶活性异常，进而引发神经肌肉疾病，证明重组蛋白技术在遗传病机制研究中的应用价值。
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4. **文献名称**：*Engineering alanyl-tRNA synthetase for efficient non-canonical amino acid incorporation*
**作者**：Wang N, Ding H, Liu W
**摘要**：通过定向进化改造重组AlaRS，使其能够高效识别非天然氨基酸，拓展了蛋白质工程中的人工氨基酸插入技术，为合成生物学工具开发提供新策略。
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注：以上文献信息为示例性质，具体内容需根据实际文献调整。建议通过PubMed或Web of Science以关键词“AlaRS recombinant”或“alanyl-tRNA synthetase expression”检索最新研究。
**Background of AlaRS Recombinant Protein**
Alanyl-tRNA synthetase (AlaRS) is a member of the aminoacyl-tRNA synthetase (aaRS) family, enzymes essential for protein synthesis. It catalyzes the attachment of alanine to its cognate tRNA (tRNA^Ala) through a two-step reaction: activating alanine with ATP to form alanyl-adenylate, followed by transferring the amino acid to the tRNA. This process ensures the accurate translation of genetic codes into functional proteins. AlaRS is highly conserved across evolution, reflecting its critical role in maintaining translational fidelity. Structurally, it comprises a catalytic domain, tRNA-binding domain, and editing domain, the latter of which corrects mischarged tRNAs to prevent errors in protein synthesis.
Recombinant AlaRS is produced via genetic engineering, typically by expressing the cloned *AlaRS* gene in bacterial (e.g., *E. coli*), yeast, or mammalian systems. This allows large-scale, pure protein production for research and industrial applications. Recombinant AlaRS is pivotal in studying enzyme kinetics, substrate specificity, and mechanisms of proofreading. It also serves as a tool to investigate diseases linked to aaRS dysfunction, such as Charcot-Marie-Tooth neuropathy, where AlaRS mutations impair neuronal function.
Additionally, AlaRS has biomedical relevance. Its editing domain is a target for antibiotic development, as disrupting bacterial aaRS activity can inhibit pathogen growth. In eukaryotes, aberrant AlaRS interactions with cellular components may contribute to autoimmune disorders. Recombinant variants enable high-throughput screening for inhibitors or modulators, aiding drug discovery. Beyond this, studies on AlaRS shed light on evolutionary biology, as ancient aaRS enzymes are hypothesized to have played roles in early life processes. Overall, recombinant AlaRS bridges fundamental research and therapeutic innovation, underscoring its importance in molecular and biomedical sciences.
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