5VF6
Crystal structure of single chain variable fragment (scFv45).
Summary for 5VF6
| Entry DOI | 10.2210/pdb5vf6/pdb |
| Descriptor | single chain variable fragment (2 entities in total) |
| Functional Keywords | single chain variable fragment, scfv, conformation-sensor antibodies, intrabodies, immune system |
| Biological source | Gallus gallus |
| Total number of polymer chains | 1 |
| Total formula weight | 25559.52 |
| Authors | Shrestha, O.K.,Tocilj, A.,Joshua-Tor, L.,Tonks, N.K. (deposition date: 2017-04-06, release date: 2018-01-31, Last modification date: 2024-10-09) |
| Primary citation | Krishnan, N.,Bonham, C.A.,Rus, I.A.,Shrestha, O.K.,Gauss, C.M.,Haque, A.,Tocilj, A.,Joshua-Tor, L.,Tonks, N.K. Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development. Nat Commun, 9:283-283, 2018 Cited by PubMed Abstract: The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity. PubMed: 29348454DOI: 10.1038/s41467-017-02252-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.635 Å) |
Structure validation
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