6ZRV
Crystal Structure of Stabilized Active Plasminogen Activator Inhibitor-1 (PAI-1-W175F) in Complex with an Inhibitory Nanobody (VHH-s-a93, Nb93)
Summary for 6ZRV
| Entry DOI | 10.2210/pdb6zrv/pdb |
| Descriptor | Plasminogen activator inhibitor 1, VHH-s-a93 (Nb93) (3 entities in total) |
| Functional Keywords | plasminogen activator inhibitor-1, pai-1, pai-1-w175f, serpin, serine protease inhibitor, nanobody, antibody fragment, protein complex, hydrolase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 56032.46 |
| Authors | Sillen, M.,Weeks, S.D.,Strelkov, S.V.,Declerck, P.J. (deposition date: 2020-07-15, release date: 2020-08-26, Last modification date: 2024-10-16) |
| Primary citation | Sillen, M.,Weeks, S.D.,Strelkov, S.V.,Declerck, P.J. Structural Insights into the Mechanism of a Nanobody That Stabilizes PAI-1 and Modulates Its Activity. Int J Mol Sci, 21:-, 2020 Cited by PubMed Abstract: Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of tissue-type (tPA) and urokinase-type (uPA) plasminogen activators (PAs). Apart from being critically involved in fibrinolysis and wound healing, emerging evidence indicates that PAI-1 plays an important role in many diseases, including cardiovascular disease, tissue fibrosis, and cancer. Targeting PAI-1 is therefore a promising therapeutic strategy in PAI-1 related pathologies. Despite ongoing efforts no PAI-1 inhibitors were approved to date for therapeutic use in humans. A better understanding of the molecular mechanisms of PAI-1 inhibition is therefore necessary to guide the rational design of PAI-1 modulators. Here, we present a 1.9 Å crystal structure of PAI-1 in complex with an inhibitory nanobody VHH-s-a93 (Nb93). Structural analysis in combination with biochemical characterization reveals that Nb93 directly interferes with PAI-1/PA complex formation and stabilizes the active conformation of the PAI-1 molecule. PubMed: 32824134DOI: 10.3390/ijms21165859 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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