6VEP
Human insulin in complex with the human insulin microreceptor in turn in complex with Fv 83-7
Summary for 6VEP
| Entry DOI | 10.2210/pdb6vep/pdb |
| Descriptor | Insulin chain A, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total) |
| Functional Keywords | hormone, hormone receptor-hormone-immune system complex, hormone receptor/hormone/immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 24 |
| Total formula weight | 299392.02 |
| Authors | Lawrence, M.C.,Menting, J.G.T. (deposition date: 2020-01-02, release date: 2020-06-03, Last modification date: 2024-10-23) |
| Primary citation | Xiong, X.,Menting, J.G.,Disotuar, M.M.,Smith, N.A.,Delaine, C.A.,Ghabash, G.,Agrawal, R.,Wang, X.,He, X.,Fisher, S.J.,MacRaild, C.A.,Norton, R.S.,Gajewiak, J.,Forbes, B.E.,Smith, B.J.,Safavi-Hemami, H.,Olivera, B.,Lawrence, M.C.,Chou, D.H. A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. Nat.Struct.Mol.Biol., 27:615-624, 2020 Cited by PubMed Abstract: Human insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins-a human des-octapeptide insulin analog-as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24-PheB25-TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development. PubMed: 32483339DOI: 10.1038/s41594-020-0430-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
Download full validation report
