{"product_id":"e3-ligase-vcb-vhl-eloc-elob","title":"Recombinant \u003cb\u003eVCB\u003c\/b\u003e Trimeric complex: VHL(M54-D213):EloC(M17-C112):EloB(M17-C112)","description":"\u003cp\u003e\u003cmeta charset=\"UTF-8\"\u003e \u003cmeta content=\"width=device-width, initial-scale=1.0\" name=\"viewport\"\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. 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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\u003cdiv class=\"info-column\"\u003e\n\u003cul class=\"custom-list\"\u003e\n\u003cli\u003eCrystallizable\u003c\/li\u003e\n\u003cli\u003eSmartSoak  \u003csup\u003e®\u003c\/sup\u003e   established\u003c\/li\u003e\n\u003cli\u003eSmartSoak  \u003csup\u003e®\u003c\/sup\u003e   hits available\u003c\/li\u003e\n\u003cli\u003ePurity \u0026gt; 95%\u003c\/li\u003e\n\u003cli\u003eMonodisperse\u003c\/li\u003e\n\u003cli\u003eMelting temperature of 44°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\u003eThe human VCB protein complex is part of the multi-subunit E3 ubiquitin ligase complex CRL2\u003csup\u003eVHL\u003c\/sup\u003e, which plays a critical role in the ubiquitin-proteasome pathway, specifically in the recognition and marking of target proteins for degradation. VCB is mediating the substrate recognition and is therefore a common target of Proteolysis-Targeting Chimeras (PROTACs), which 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 VCB and a protein of interest.\u003cbr\u003eOur recombinant VCB protein is of high, crystallography-grade quality and is well suited for researchers pursuing the development of novel PROTAC strategies.\u003c\/p\u003e\n\u003c\/div\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\u003eThe three proteins that form the VCB complex were expressed in parallel under three different promoters on two plasmids. The VCB complex is formed by von Hippel–Lindau protein (VHL) spanning residues G_M54-D213 with an additional N-terminal G remaining from the TEV cleavage. VHL forms a complex with ElonginB (M1-K104) and ElonginC (M17-C112).\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\"\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 G_VHL(M54-D213):EloC(M17-C112):EloB(M17-C112)\u003cbr\u003e\u003cb\u003eSource:\u003c\/b\u003e Human\u003cbr\u003e\u003cb\u003eExpression Host:\u003c\/b\u003e \u003ci\u003eEscherichia coli\u003c\/i\u003e\u003cbr\u003e\u003cb\u003eMolecular weight [kDa]:\u003c\/b\u003e 41.1\u003cbr\u003e\u003cb\u003epI:\u003c\/b\u003e 5.92\u003cbr\u003e\u003cb\u003eExtinction Coefficient [M\u003csup\u003e-1\u003c\/sup\u003ecm\u003csup\u003e-1\u003c\/sup\u003e]:\u003c\/b\u003e 25900\u003cbr\u003e\u003cb\u003eConcentration:\u003c\/b\u003e 10.2 mg\/mL\u003cbr\u003e\u003cb\u003eStorage Buffer:\u003c\/b\u003e 20 mM HEPES; pH 7.5, 100 mM NaCl, 1 mM DTT \u003cbr\u003e\u003cb\u003eTag:\u003c\/b\u003e none\u003c\/p\u003e\n\u003cp style=\"margin-top: 15px;\"\u003e\u003cb\u003eAmino acid sequence:\u003c\/b\u003e\u003c\/p\u003e\n\u003cdiv class=\"sequence-box\"\u003eGMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGDMYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEVNFREIPSHVLSKVCMYFTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDCMDVFLMIRRHKTTIFTDAKESSTVFELKRIVEGILKRPPDEQRLYKDDQLLDDGKTLGECGFTSQTARPQAPATVGLAFRADDTFEALCIEPFSSPPELPDVMK\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\/VCB_datasheet.pdf?v=1774029376\" 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 3.2\u003cbr\u003e\u003cb\u003ePolydispersity Index (PDI): \u003c\/b\u003e 0.11\u003cbr\u003e\u003cb\u003eT\u003csub\u003eon\u003c\/sub\u003e (°C):\u003c\/b\u003e 26.8\u003cbr\u003e\u003cb\u003eT\u003csub\u003em\u003c\/sub\u003e (°C):\u003c\/b\u003e 43.9\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\u003eVCB is the substrate receptor of the Cullin-RING E3 ubiquitin ligase CRL2\u003csup\u003eVHL\u003c\/sup\u003e and plays an important role in the Oxygen-Sensing pathway by regulating transcription factor hypoxia-inducible factor (HIF)-1ɑ through ubiquitin transfer and proteasomal degradation. The full E3 ligase is a large, pentameric protein complex build up by trimeric VCB, the scaffold protein Cullin-2 and the RING finger subunit Rbx1.\u003cbr\u003e The VCB complex itself consists of the von Hippel-Lindau protein (VHL) and the two adaptor proteins ElonginC (EloC) and ElonginB (EloB). VHL serves as the central substrate binding module and features a hydroxyproline (Hyp) substrate recognition site as well as a binding domain that interacts with EloC. The binding of VHL to the N-terminal region of Cullin-2 and the stabilization of the complex is mediated by the two adaptor proteins EloC and EloB.\u003c\/p\u003e\n\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/image2.png?v=1773751659\" alt=\"Architecture of the Cullin-RING E3 ligase system CRL2VHL with VCB binding to Cullin-2.\" style=\"max-width: 100%; height: auto; margin-top: 20px;\" class=\"responsive-img\"\u003e\n\u003cp style=\"font-size: 16px;\"\u003eFigure 1: Architecture of the Cullin-RING E3 ligase system CRL2VHL with VCB binding to Cullin-2. Adapted from (Cardote et al., 2017)\u003c\/p\u003e\n\u003cbr\u003e\n\u003ch4\u003eVCB Success in Smart-Soak Campaign\u003c\/h4\u003e\n\u003cp\u003eVCB serves as a critical component in PROTAC design by recruiting the target proteins via its central substrate binding module VHL. Formation of a ternary complex involving the target protein is required for targeted protein degradation (TPD). There is a need for novel chemical matter for recruitment of target proteins via VHL. Enhanced molecular characteristics of next-generation VHL binders could broaden the efficacy of VCB-mediated TPD. \u003cbr\u003e\u003cbr\u003eAfter crystallizing the VCB complex, a SmartSoak system was set up and it was observed that SmartSoak improves the diffraction of the crystal by 0.5 Ångström. Subsequently, an in-house fragment library was SmartSoak'ed and novel VCB binders could be identified: Four binders at EloC, one binder at the EloC-EloB interface (cryptic pocket) and three binders at VHL (cryptic and orthosteric). \u003cbr\u003e\u003cbr\u003eInterestingly, two fragments bind at the cryptic pocket of VHL, inducing a more pronounced opening of the pocket compared to the published structures. The two fragments are well-positioned for linking.\u003c\/p\u003e\n\u003cimg src=\"https:\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/SmartSoak_-enabled_soaking_system_identifies_allosteric_and_orthosteric_binders_of_the_VCB_complex.png?v=1774517499\" alt=\"binders of the VCB complex\" style=\"max-width: 100%; height: auto; margin-top: 20px;\" class=\"responsive-img\"\u003e\n\u003cp style=\"font-size: 16px;\"\u003eFigure 2: SmartSoak® -enabled soaking system identifies allosteric and orthosteric binders of the VCB complex.\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 \u003cbr\u003eCardote, Teresa A. F., Gadd, Morgan S., Ciulli, Alessio. (2017). Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex. Cell Press. DOI: \u003ca href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28591624\/\" target=\"_blank\"\u003e10.1016\/j.str.2017.04.009\u003c\/a\u003e\u003cbr\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e","brand":"CrystalsFirst Shop","offers":[{"title":"1 mg","offer_id":57039360328063,"sku":null,"price":1500.0,"currency_code":"EUR","in_stock":true},{"title":"5 mg","offer_id":57039360360831,"sku":null,"price":6750.0,"currency_code":"EUR","in_stock":true},{"title":"10 mg","offer_id":57039360393599,"sku":null,"price":12000.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0958\/0612\/8511\/files\/VCB-purple.jpg?v=1778612755","url":"https:\/\/shop.crystalsfirst.com\/products\/e3-ligase-vcb-vhl-eloc-elob","provider":"CrystalsFirst GmbH","version":"1.0","type":"link"}