4UIP
The complex structure of extracellular domain of EGFR with Repebody (rAC1).
Summary for 4UIP
| Entry DOI | 10.2210/pdb4uip/pdb |
| Descriptor | EPIDERMAL GROWTH FACTOR RECEPTOR, REPEBODY (RAC1), 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | transferase |
| Biological source | HOMO SAPIENS (HUMAN) More |
| Total number of polymer chains | 2 |
| Total formula weight | 97757.03 |
| Authors | Kang, Y.J.,Cha, Y.J.,Cho, H.S.,Lee, J.J.,Kim, H.S. (deposition date: 2015-03-31, release date: 2015-11-25, Last modification date: 2024-11-06) |
| Primary citation | Lee, J.,Choi, H.,Yun, M.,Kang, Y.,Jung, J.,Ryu, Y.,Kim, T.Y.,Cha, Y.,Cho, H.,Min, J.,Chung, C.,Kim, H. Enzymatic Prenylation and Oxime Ligation for the Synthesis of Stable and Homogeneous Protein-Drug Conjugates for Targeted Therapy. Angew.Chem.Int.Ed.Engl., 54:12020-, 2015 Cited by PubMed Abstract: Targeted therapy based on protein-drug conjugates has attracted significant attention owing to its high efficacy and low side effects. However, efficient and stable drug conjugation to a protein binder remains a challenge. Herein, a chemoenzymatic method to generate highly stable and homogenous drug conjugates with high efficiency is presented. The approach comprises the insertion of the CaaX sequence at the C-terminal end of the protein binder, prenylation using farnesyltransferase, and drug conjugation through an oxime ligation reaction. MMAF and an EGFR-specific repebody are used as the antitumor agent and protein binder, respectively. The method enables the precisely controlled synthesis of repebody-drug conjugates with high yield and homogeneity. The utility of this approach is illustrated by the notable stability of the repebody-drug conjugates in human plasma, negligible off-target effects, and a remarkable antitumor activity in vivo. The present method can be widely used for generating highly homogeneous and stable PDCs for targeted therapy. PubMed: 26315561DOI: 10.1002/ANIE.201505964 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.95 Å) |
Structure validation
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