6zrv

Crystal Structure of Stabilized Active Plasminogen Activator Inhibitor-1 (PAI-1-W175F) in Complex with an Inhibitory Nanobody (VHH-s-a93, Nb93)

spinqualitylabelsall models 6zrv, resolution 1.88Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6zrv is a 2 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.88Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 A 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. Structural Insights into the Mechanism of a Nanobody That Stabilizes PAI-1 and Modulates Its Activity.,Sillen M, Weeks SD, Strelkov SV, Declerck PJ Int J Mol Sci. 2020 Aug 15;21(16):5859. doi: 10.3390/ijms21165859. PMID:32824134 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Plasminogen activator inhibitor

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