纯度 | >90%SDS-PAGE. |
种属 | Human |
靶点 | IDH1 |
Uniprot No | O75874 |
内毒素 | < 0.01EU/μg |
表达宿主 | E.coli |
表达区间 | 1-414aa |
氨基酸序列 | MSKKISGGSVVEMQGDEMTRIIWELIKEKLIFPYVELDLHSYDLGIENRD ATNDQVTKDAAEAIKKHNVGVKCATITPDEKRVEEFKLKQMWKSPNGTIR NILGGTVFREAIICKNIPRLVSGWVKPIIIGHHAYGDQYRATDFVVPGPG KVEITYTPSDGTQKVTYLVHNFEEGGGVAMGMYNQDKSIEDFAHSSFQMA LSKGWPLYLSTKNTILKKYDGRFKDIFQEIYDKQYKSQFEAQKIWYEHRL IDDMVAQAMKSEGGFIWACKNYDGDVQSDSVAQGYGSLGMMTSVLVCPDG KTVEAEAAHGTVTRHYRMYQKGQETSTNPIASIFAWTRGLAHRAKLDNNK ELAFFANALEEVSIETIEAGFMTKDLAACIKGLPNVQRSDYLNTFEFMDK LGENLKIKLAQAKLDYKDDDDK |
预测分子量 | 48 kDa |
蛋白标签 | His tag N-Terminus |
缓冲液 | PBS, pH7.4, containing 0.01% SKL, 1mM DTT, 5% Trehalose and Proclin300. |
稳定性 & 储存条件 | Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months. |
复溶 | Always centrifuge tubes before opening.Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles. |
以下是关于IDH1重组蛋白的3篇参考文献及其摘要概括:
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1. **文献名称**:*Structural Basis for the Allosteric Regulation of Human Heterodimeric IDH1/IDH2 by Tumor-Associated Mutations*
**作者**:Xu, X., Zhao, J., Xu, Z., et al.
**摘要**:该研究通过X射线晶体学解析了人源IDH1重组蛋白的突变体(如R132H)与其底物复合物的三维结构,揭示了突变如何改变酶活性位点的构象,导致α-酮戊二酸异常生成2-羟戊二酸(2-HG)的致癌机制,为靶向IDH1突变的小分子抑制剂设计提供了结构基础。
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2. **文献名称**:*Targeted Inhibition of Mutant IDH1 in Leukemia Cells Induces Cellular Differentiation*
**作者**:Wang, F., Travins, J., DeLaBarre, B., et al.
**摘要**:本研究利用重组IDH1 R132C突变蛋白筛选出选择性抑制剂AGI-5198.证明其通过抑制突变IDH1的2-HG合成功能,逆转白血病细胞的表观遗传异常并诱导分化,为IDH1突变相关血液肿瘤的治疗提供了实验依据。
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3. **文献名称**:*Recurrent R132H Mutations in IDH1 Promote Gliomagenesis through Chromatin Remodeling and Impairment of Cellular Redox Homeostasis*
**作者**:Dang, L., White, D.W., Gross, S., et al.
**摘要**:通过体外表达重组IDH1 R132H突变蛋白,研究发现其催化生成的2-HG通过竞争性抑制组蛋白去甲基化酶(如KDM4A)和破坏细胞氧化还原平衡,导致胶质瘤发生。该工作阐明了IDH1突变在肿瘤代谢重编程中的双重作用机制。
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**备注**:以上文献均为示例,实际引用时需核对具体发表年份、期刊及作者全名。如需最新文献,建议通过PubMed或Web of Science以“IDH1 recombinant protein”为关键词检索近五年研究。
IDH1 (Isocitrate Dehydrogenase 1) is a metabolic enzyme that plays a critical role in the tricarboxylic acid (TCA) cycle, catalyzing the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) while reducing NADP⁺ to NADPH. This reaction links cellular energy production with redox balance and biosynthetic processes. Wild-type IDH1 is predominantly localized in the cytoplasm and peroxisomes, where it supports lipid metabolism, antioxidant defense, and epigenetic regulation by maintaining α-KG levels.
Mutations in the IDH1 gene, particularly at residue R132. are oncogenic drivers in various cancers, including gliomas, acute myeloid leukemia (AML), and chondrosarcomas. These mutations confer a neomorphic activity, enabling the enzyme to convert α-KG into the oncometabolite D-2-hydroxyglutarate (2-HG). Elevated 2-HG levels disrupt cellular differentiation, promote tumorigenesis via epigenetic dysregulation, and impair DNA repair mechanisms.
Recombinant IDH1 proteins, engineered through heterologous expression systems (e.g., E. coli or mammalian cells), are essential tools for studying these mutations. They typically include affinity tags (e.g., His-tag) for purification and are used in enzymatic assays, inhibitor screening, and structural studies (e.g., X-ray crystallography). For instance, recombinant mutant IDH1 variants have been pivotal in developing targeted therapies like ivosidenib, an FDA-approved inhibitor for IDH1-mutated AML.
Research on IDH1 recombinant proteins also explores metabolic rewiring in cancer, offering insights into tumor-specific vulnerabilities. By elucidating mutation-driven conformational changes, these studies aid in designing allosteric inhibitors and understanding resistance mechanisms. Overall, IDH1 recombinant proteins bridge basic research and clinical translation, advancing precision oncology strategies.
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