5VTA
Co-Crystal Structure of DPPIV with a Chemibody Inhibitor
Summary for 5VTA
| Entry DOI | 10.2210/pdb5vta/pdb |
| Related | 4FFV 4FFW |
| Descriptor | Dipeptidyl peptidase 4, Fab light chain, Fab heavy chain, ... (9 entities in total) |
| Functional Keywords | hydrolase, chemibody |
| Biological source | Rattus norvegicus (Rat) More |
| Total number of polymer chains | 12 |
| Total formula weight | 535923.46 |
| Authors | Wang, Z.,Johnstone, S.,Cheng, A. (deposition date: 2017-05-16, release date: 2018-05-09, Last modification date: 2024-11-13) |
| Primary citation | Cheng, A.C.,Doherty, E.M.,Johnstone, S.,DiMauro, E.F.,Dao, J.,Luthra, A.,Ye, J.,Tang, J.,Nixey, T.,Min, X.,Tagari, P.,Miranda, L.P.,Wang, Z. Structure-guided Discovery of Dual-recognition Chemibodies. Sci Rep, 8:7570-7570, 2018 Cited by PubMed Abstract: Small molecules and antibodies each have advantages and limitations as therapeutics. Here, we present for the first time to our knowledge, the structure-guided design of "chemibodies" as small molecule-antibody hybrids that offer dual recognition of a single target by both a small molecule and an antibody, using DPP-IV enzyme as a proof of concept study. Biochemical characterization demonstrates that the chemibodies present superior DPP-IV inhibition compared to either small molecule or antibody component alone. We validated our design by successfully solving a co-crystal structure of a chemibody in complex with DPP-IV, confirming specific binding of the small molecule portion at the interior catalytic site and the Fab portion at the protein surface. The discovery of chemibodies presents considerable potential for novel therapeutics that harness the power of both small molecule and antibody modalities to achieve superior specificity, potency, and pharmacokinetic properties. PubMed: 29765112DOI: 10.1038/s41598-018-25848-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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