{"product_id":"recombinant-b-crbn-ddb1-complex-b-cereblon-e3-ligase","title":"Recombinant \u003cb\u003eHis-tagged DDB1(M1-H1140)\/CRBN(M1-L442) Complex\u003c\/b\u003e Cereblon, E3 Ligase","description":"\u003cp\u003e\u003cmeta charset=\"UTF-8\"\u003e \u003cmeta name=\"viewport\" content=\"width=device-width, initial-scale=1.0\"\u003e\u003c\/p\u003e\n\u003cstyle\u003e\n    \/* 1. VARIABLEN \u0026 RESET *\/\n    :root {\n        --primary-color: #0dbaad;\n        --text-dark: #373636;\n        --border-light: #e0e0e0;\n    }\n\n    * { margin: 0; padding: 0; box-sizing: border-box; }\n\n    .container {\n        max-width: 1200px;\n        margin: 0 auto;\n        background-color: white;\n        padding: 20px;\n        font-family: \"Source Sans Pro\", sans-serif;\n        color: var(--text-dark);\n        line-height: 1.6;\n    }\n\n    \/* 2. TOP SEKTION (Tabelle \u0026 Bild) *\/\n    .product-top-section {\n        display: flex;\n        flex-wrap: wrap;\n        gap: 30px;\n        align-items: flex-start; \n        justify-content: center;\n        margin-bottom: 30px;\n    }\n\n    \/* SALES HINWEIS STYLING *\/\n    .sales-notice-container {\n        width: 100%;\n        margin-bottom: 20px;\n    }\n    .sales-notice {\n        font-size: 20px;\n        font-weight: 400;\n        text-align: center;\n        margin: 15px 0;\n        color: var(--text-dark);\n    }\n    .sales-notice a {\n        color: var(--primary-color);\n        text-decoration: none;\n        font-weight: 400;\n    }\n    .sales-notice a:hover {\n        opacity: 0.8;\n    }\n    .sales-hr {\n        margin: 15px 0;\n        height: 2px;\n        background-color: var(--primary-color);\n        border: none;\n        width: 100%;\n    }\n\n    .info-column {\n        flex: 1.5;\n        min-width: 280px;\n    }\n\n    .image-column {\n        flex: 1;\n        min-width: 250px;\n        display: flex;\n        justify-content: center;\n        align-items: flex-start;\n    }\n\n    .side-image {\n        max-width: 240px;\n        height: auto;\n        display: block;\n        margin-top: -25px; \/* Desktop-Lift *\/\n    }\n\n    \/* 3. LISTE MIT TÜRKISEN HÄKCHEN *\/\n    .custom-list {\n        list-style: none;\n        padding-left: 0;\n        font-size: 22px;\n    }\n    .custom-list li {\n        margin-bottom: 12px;\n        display: flex;\n        align-items: center;\n    }\n    .custom-list li::before {\n        content: \"\\2714\"; \n        color: var(--primary-color) !important;\n        font-weight: bold;\n        margin-right: 15px;\n        flex-shrink: 0;\n        font-size: 1.3em;\n    }\n\n    hr { margin: 30px 0; height: 2px; background-color: var(--primary-color); border: none; }\n\n    \/* 4. AKKORDEON \u0026 INNEN-ÜBERSCHRIFTEN *\/\n    .accordion-container {\n        border-top: 1px solid var(--border-light);\n        margin: 20px 0;\n    }\n    .accordion-item {\n        border-bottom: 1px solid var(--border-light);\n    }\n    .accordion-header {\n        width: 100%;\n        padding: 20px 0;\n        background: none;\n        border: none;\n        display: flex;\n        justify-content: space-between;\n        align-items: center;\n        font-family: inherit;\n        font-size: 25px;\n        color: var(--primary-color) !important; \/* Türkis für Haupt-Header *\/\n        text-transform: uppercase;\n        cursor: pointer;\n        text-align: left;\n    }\n\n    \/* Styling für h4 Überschriften im Scientific Context *\/\n    .content-inner h4 {\n        color: var(--primary-color) !important;\n        text-transform: uppercase;\n        margin: 20px 0 10px 0;\n        font-size: 20px;\n    }\n\n    .icon { position: relative; width: 20px; height: 20px; flex-shrink: 0; margin-left: 10px; }\n    .icon::before, .icon::after {\n        content: '';\n        position: absolute;\n        background-color: currentColor;\n        transition: transform 0.3s ease;\n    }\n    .icon::before { width: 100%; height: 2px; top: 50%; left: 0; transform: translateY(-50%); }\n    .icon::after { width: 2px; height: 100%; left: 50%; top: 0; transform: translateX(-50%); }\n    .accordion-item.active .icon::after { transform: translateX(-50%) rotate(90deg); opacity: 0; }\n\n    .accordion-content {\n        max-height: 0;\n        overflow: hidden;\n        transition: max-height 0.5s cubic-bezier(0, 1, 0, 1);\n    }\n    .accordion-item.active .accordion-content {\n        max-height: 4000px;\n        transition: max-height 1s ease-in-out;\n    }\n    .content-inner { padding: 15px 0 35px 0; font-size: 19px; }\n\n    .sequence-box {\n        word-break: break-all;\n        font-family: monospace;\n        background: #f4f4f4;\n        padding: 15px;\n        font-size: 15px;\n        border-left: 4px solid var(--primary-color);\n        margin-top: 10px;\n    }\n\n    \/* 5. MOBILE ANPASSUNGEN *\/\n    @media (max-width: 600px) {\n        .product-top-section {\n            flex-direction: column;\n            align-items: center;\n        }\n        .image-column {\n            order: -1;\n            margin-bottom: 20px;\n            width: 100%;\n        }\n        .side-image {\n            margin-top: 0;\n            margin-left: auto;\n            margin-right: auto;\n        }\n        .custom-list { font-size: 17px; }\n        .accordion-header { font-size: 20px; }\n    }\n    \/* 6. INTRO TEXT SEKTION *\/\n    .intro-section {\n        margin: 20px 0;\n        font-size: 19px; \/* Desktop Größe *\/\n        line-height: 1.8;\n    }\n\n    \/* Mobile Anpassung für den Intro-Text *\/\n    @media (max-width: 600px) {\n        .intro-section {\n            font-size: 17px; \n            text-align: left;\n            padding: 0 5px;\n        }\n    }\n  \n\u003c\/style\u003e\n\u003cdiv class=\"container\"\u003e\n\u003cdiv class=\"product-top-section\"\u003e\n\n\u003cdiv class=\"sales-notice-container\"\u003e\n    \u003chr class=\"sales-hr\"\u003e\n    \u003cp class=\"sales-notice\"\u003eFor smaller amounts please \u003ca href=\"https:\/\/shop.crystalsfirst.com\/pages\/contact\"\u003econtact our sales team.\u003c\/a\u003e\u003c\/p\u003e\n    \u003chr class=\"sales-hr\"\u003e\n\u003c\/div\u003e\n  \n\u003cdiv class=\"info-column\"\u003e\n\u003cul class=\"custom-list\"\u003e\n\u003cli\u003eCrystallizable\u003c\/li\u003e\n\u003cli\u003ePurity \u0026gt; 95%\u003c\/li\u003e\n\u003cli\u003eMelting temperature of 55°C\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"image-column\"\u003e\u003cimg class=\"side-image\" alt=\"Quality Plus Siegel\" src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/Stempel-QUALITY-PLUS-new.png?v=1771953936\"\u003e\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr\u003e\n\u003cdiv class=\"intro-section\"\u003e\n\u003cp\u003e\u003c\/p\u003e\n\u003cp\u003eOur recombinant DDB1-CRBN protein is of high, crystallography-grade quality and is well suited for researchers pursuing the development of novel PROTAC strategies. Addition of a Phenyl-Dihydrouracile (PDHU) shifts the melting temperature T\u003csub\u003em\u003c\/sub\u003e of our DDB1-CRBN by 2.45 °C, suggesting structural integrity and ligand accessibility of the CRBN binding pocket. In addition we could verify that the complex is heterodimeric by structural analysis using X-ray crystallography.\u003cbr\u003e\u003cbr\u003e\nThe ubiquitin E3 ligase Cereblon (CRBN) is part of the ubiquitin–proteasome system and a common target of small-molecule therapeutics. PROTACs have rapidly emerged as a leading modality in proximity-based therapeutics, leveraging the ubiquitin–proteasome system to eliminate proteins by enforcing proximity between an E3 ligase like CRBN and a protein of interest.\n\u003c\/p\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-container\"\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003econstruct design\u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003eHi5 insect cells were co-transfected with His_Flag_Tev_CRBN(M1-L442) and DDB1(M1-H1140). DDB1 acts as a stabilizing binding partner that mediates solubility of CRBN during expression and purification. The formation of the heterodimeric DDB1\/CRBN complex was confirmed by structural analysis using X-ray crystallography. The His_Flag_Tag remains in the final product and does not interfere with crystallization or interaction of the protein with a Phenyl-Dihydrouracile (PDHU) reference compound.\u003c\/p\u003e\n\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eProtein Properties \u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003e\u003cb\u003eProtein Construct:\u003c\/b\u003e DDB1(M1-H1140)\/His-Flag-Tev-CRBN(M1-L442)\u003cbr\u003e\u003cb\u003eSource:\u003c\/b\u003e Human\u003cbr\u003e\u003cb\u003eExpression Host:\u003c\/b\u003e \u003ci\u003eTrichoplusia ni (Hi5)\u003c\/i\u003e\u003cbr\u003e\u003cb\u003eMolecular weight:\u003c\/b\u003e 127 kDa (DDB1); 51 kDa(CRBN)\u003cbr\u003e\u003cb\u003epI:\u003c\/b\u003e 5.57 (DDB1); 5.14 (CRBN)\u003cbr\u003e\u003cb\u003eExtinction Coefficient:\u003c\/b\u003e 126966 M\u003csup\u003e-1\u003c\/sup\u003ecm\u003csup\u003e-1\u003c\/sup\u003e (DDB1); 71850 M\u003csup\u003e-1\u003c\/sup\u003ecm\u003csup\u003e-1\u003c\/sup\u003e (CRBN)\u003cbr\u003e\u003cb\u003eConcentration:\u003c\/b\u003e 19.8 mg\/mL\u003cbr\u003e\u003cb\u003eStorage Buffer:\u003c\/b\u003e 50 mM HEPES pH 7.4, 200 mM NaCl, 0.5 mM TCEP \u003cbr\u003e\u003cb\u003eTag:\u003c\/b\u003e His_Flag_Tev\u003c\/p\u003e\n\u003cp style=\"margin-top: 15px;\"\u003e\u003cb\u003eAmino acid sequence DDB1:\u003c\/b\u003e\u003c\/p\u003e\n\u003cdiv class=\"sequence-box\"\u003eMSYNYVVTAQKPTAVNGCVTGHFTSAEDLNLLIAKNTRLEIYVVTAEGLRPVKEVGMYGKIAVMELFRPKGESKDLLFILTAKYNACILEYKQSGESIDIITRAHGNVQDRIGRPSETGIIGIIDPECRMIGLRLYDGLFKVIPLDRDNKELKAFNIRLEELHVIDVKFLYGCQAPTICFVYQDPQGRHVKTYEVSLREKEFNKGPWKQENVEAEASMVIAVPEPFGGAIIIGQESITYHNGDKYLAIAPPIIKQSTIVCHNRVDPNGSRYLLGDMEGRLFMLLLEKEEQMDGTVTLKDLRVELLGETSIAECLTYLDNGVVFVGSRLGDSQLVKLNVDSNEQGSYVVAMETFTNLGPIVDMCVVDLERQGQGQLVTCSGAFKEGSLRIIRNGIGIHEHASIDLPGIKGLWPLRSDPNRETDDTLVLSFVGQTRVLMLNGEEVEETELMGFVDDQQTFFCGNVAHQQLIQITSASVRLVSQEPKALVSEWKEPQAKNISVASCNSSQVVVAVGRALYYLQIHPQELRQISHTEMEHEVACLDITPLGDSNGLSPLCAIGLWTDISARILKLPSFELLHKEMLGGEIIPRSILMTTFESSHYLLCALGDGALFYFGLNIETGLLSDRKKVTLGTQPTVLRTFRSLSTTNVFACSDRPTVIYSSNHKLVFSNVNLKEVNYMCPLNSDGYPDSLALANNSTLTIGTIDEIQKLHIRTVPLYESPRKICYQEVSQCFGVLSSRIEVQDTSGGTTALRPSASTQALSSSVSSSKLFSSSTAPHETSFGEEVEVHNLLIIDQHTFEVLHAHQFLQNEYALSLVSCKLGKDPNTYFIVGTAMVYPEEAEPKQGRIVVFQYSDGKLQTVAEKEVKGAVYSMVEFNGKLLASINSTVRLYEWTTEKELRTECNHYNNIMALYLKTKGDFILVGDLMRSVLLLAYKPMEGNFEEIARDFNPNWMSAVEILDDDNFLGAENAFNLFVCQKDSAATTDEERQHLQEVGLFHLGEFVNVFCHGSLVMQNLGETSTPTQGSVLFGTVNGMIGLVTSLSESWYNLLLDMQNRLNKVIKSVGKIEHSFWRSFHTERKTEPATGFIDGDLIESFLDISRPKMQEVVANLQYDDGSGMKREATADDLIKVVEELTRIH\u003c\/div\u003e\n\u003cp style=\"margin-top: 15px;\"\u003e\u003cb\u003eAmino acid sequence His_Flag_Tev_CRBN:\u003c\/b\u003e\u003c\/p\u003e\n\u003cdiv class=\"sequence-box\"\u003eMHHHHHHGSHHDYKDDDDKENLYFQSMAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eQuality Plus\u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003cp\u003e\u003cb\u003eQC Data:\u003c\/b\u003e \u003ca href=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/DDB1_CRBN_datasheet_Lot185.pdf?v=1784292858\" target=\"_blank\"\u003eDatasheet\u003c\/a\u003e\u003cbr\u003e\u003cb\u003ePurity SDS:\u003c\/b\u003e \u0026gt;95 % \u003cbr\u003e\u003cb\u003eHydrodynamic Radius (nm):\u003c\/b\u003e 6.33\u003cbr\u003e\u003cb\u003ePolydispersity Index (PDI): \u003c\/b\u003e 0.21\u003cbr\u003e\u003cb\u003eT\u003csub\u003eon\u003c\/sub\u003e (°C):\u003c\/b\u003e 51.2\u003cbr\u003e\u003cb\u003eT\u003csub\u003em, 1\u003c\/sub\u003e (°C):\u003c\/b\u003e 55.0\u003cbr\u003e\u003cb\u003eT\u003csub\u003em, 2\u003c\/sub\u003e (°C):\u003c\/b\u003e 62.9\u003cbr\u003e\u003c\/p\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv class=\"accordion-item\"\u003e\n\u003cbutton class=\"accordion-header\"\u003eScientific context \u003cspan class=\"icon\"\u003e\u003c\/span\u003e\u003c\/button\u003e\n\u003cdiv class=\"accordion-content\"\u003e\n\u003cdiv class=\"content-inner\"\u003e\n\u003ch4\u003eStructure and function\u003c\/h4\u003e\n\u003cp\u003eCereblon (CRBN) functions as the substrate receptor of the Cullin 4–RING E3 ubiquitin ligase complex by coupling target recognition to ubiquitin transfer. CRBN is bound by the DNA damage-binding protein 1 (DDB1), which serves as an adaptor protein connecting the native CRBN to the rest of the cullin-4 E3 ubiquitin ligase complex. Through its C-terminal thalidomide-binding domain, CRBN directly engages its substrates, bringing them and ubiquitin-loaded E2 into close proximity and positioning the target for polyubiquitination.\u003cbr\u003e\u003cbr\u003e\nIts native targets include many important endogenous substrates, such as adenosine monophosphate-activated protein kinase subunit α1, amyloid precursor protein or glutamine synthetase.\n\u003c\/p\u003e\n\u003cbr\u003e\n\u003ch4\u003eCRBN as important drug target\u003c\/h4\u003e\n\u003cp\u003eCRBN and its associated E3 ubiquitin ligase are central to targeted protein degradation strategies with significant therapeutic potential. Immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide act as molecular glues that enable CRBN to recruit new substrates (neosubstrates), leading to their ubiquitination and degradation, which has diverse anti-cancer and immunmodulatory effects. \nMoreover, CRBN-binding ligands have been adapted for the development of PROTACs that induce the degradation of specific clinically relevant targets, underscoring the importance of CRBN in modern drug discovery.\n\u003c\/p\u003e\n\u003cdiv style=\"font-size: 15px; margin-top: 25px; border-top: 1px dotted #ccc; padding-top: 15px;\"\u003e\n\u003cb\u003eReferences:\u003c\/b\u003e\n   \u003cbr\u003eTao, Jing. (\u003cb\u003e2018\u003c\/b\u003e). The interacting domains in cereblon differentially modulate the immunomodulatory drug-mediated ubiquitination and degradation of its binding partners. \u003cb\u003eBiochemical and Biophysical Research Communications.\u003c\/b\u003e DOI:   \u003ca href=\"https:\/\/doi.org\/10.1016\/j.bbrc.2018.11.058\" target=\"_blank\"\u003e10.1016\/j.bpj.2021.04.015\u003c\/a\u003e\u003cbr\u003e\n \u003cbr\u003eFischer, E.S. et al. (\u003cb\u003e2014\u003c\/b\u003e). Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. \u003cb\u003eNature.\u003c\/b\u003e DOI: \u003ca href=\"https:\/\/www.nature.com\/articles\/nature13527\" target=\"_blank\"\u003e10.1038\/nature1352\u003c\/a\u003e\u003cbr\u003e\u003cbr\u003e\n  \n\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cp\u003e \u003c\/p\u003e","brand":"CrystalsFirst Shop","offers":[{"title":"500 µg","offer_id":57864793555327,"sku":null,"price":1499.0,"currency_code":"EUR","in_stock":true},{"title":"1 mg","offer_id":57858207613311,"sku":null,"price":2810.0,"currency_code":"EUR","in_stock":true},{"title":"5 mg","offer_id":57944909349247,"sku":null,"price":12000.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/CRBN-DDB1_b907e69e-7b68-4f25-b3a4-ae34cddd81ca.jpg?v=1782902800","url":"https:\/\/shop.crystalsfirst.com\/products\/recombinant-b-crbn-ddb1-complex-b-cereblon-e3-ligase","provider":"CrystalsFirst GmbH","version":"1.0","type":"link"}