6T9E
Crystal structure of a bispecific DutaFab in complex with human PDGF
This is a non-PDB format compatible entry.
Summary for 6T9E
| Entry DOI | 10.2210/pdb6t9e/pdb |
| Descriptor | DutaFab mat VH chain, DutaFab mat VL chain, Platelet-derived growth factor subunit B (3 entities in total) |
| Functional Keywords | monoclonal antibody, bispecific antibody, fab fragment, pdgf, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 119478.50 |
| Authors | Kimbung, R.,Logan, D.T.,Beckmann, R.,Jensen, K.,Speck, J.,Fenn, S.,Kettenberger, H. (deposition date: 2019-10-28, release date: 2020-12-16, Last modification date: 2024-10-16) |
| Primary citation | Beckmann, R.,Jensen, K.,Fenn, S.,Speck, J.,Krause, K.,Meier, A.,Roth, M.,Fauser, S.,Kimbung, R.,Logan, D.T.,Steegmaier, M.,Kettenberger, H. DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously. Nat Commun, 12:708-708, 2021 Cited by PubMed Abstract: We report the development of a platform of dual targeting Fab (DutaFab) molecules, which comprise two spatially separated and independent binding sites within the human antibody CDR loops: the so-called H-side paratope encompassing HCDR1, HCDR3 and LCDR2, and the L-side paratope encompassing LCDR1, LCDR3 and HCDR2. Both paratopes can be independently selected and combined into the desired bispecific DutaFabs in a modular manner. X-ray crystal structures illustrate that DutaFabs are able to bind two target molecules simultaneously at the same Fv region comprising a VH-VL heterodimer. In the present study, this platform is applied to generate DutaFabs specific for VEGFA and PDGF-BB, which show high affinities, physico-chemical stability and solubility, as well as superior efficacy over anti-VEGF monotherapy in vivo. These molecules exemplify the usefulness of DutaFabs as a distinct class of antibody therapeutics, which is currently being evaluated in patients. PubMed: 33514724DOI: 10.1038/s41467-021-20949-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.989 Å) |
Structure validation
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