4OS1
Crystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK601 (bicyclic 1)
Summary for 4OS1
| Entry DOI | 10.2210/pdb4os1/pdb |
| Related | 4GLY 4OS2 4OS4 4OS5 4OS6 4OS7 |
| Related PRD ID | PRD_001222 |
| Descriptor | Urokinase-type plasminogen activator, bicyclic peptide UK601 (bicyclic 1), SULFATE ION, ... (5 entities in total) |
| Functional Keywords | bicyclic peptide, inhibitor, protease, disulfide bridges, cyclization, extracellular, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: P00749 |
| Total number of polymer chains | 2 |
| Total formula weight | 29387.46 |
| Authors | Chen, S.,Pojer, F.,Heinis, C. (deposition date: 2014-02-12, release date: 2014-09-24, Last modification date: 2025-03-26) |
| Primary citation | Chen, S.,Gopalakrishnan, R.,Schaer, T.,Marger, F.,Hovius, R.,Bertrand, D.,Pojer, F.,Heinis, C. Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides. Nat Chem, 6:1009-1016, 2014 Cited by PubMed Abstract: The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with different biological activities. Here, we describe the development of a dithiol amino acid (Dtaa) that can form two disulfide bridges at a single amino acid site. Application of Dtaas to a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor that contain disulfide constraints enhanced their inhibitory activities 40- and 7.6-fold, respectively. X-ray crystallographic and NMR structure analysis show that the peptide ligands containing Dtaas have retained their native tertiary structures. We furthermore show that replacement of two cysteines by Dtaas can avoid the formation of disulfide bond isomers. With these properties, Dtaas are likely to have broad application in the rational design or directed evolution of peptides and proteins with high activity and stability. PubMed: 25343607DOI: 10.1038/nchem.2043 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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