5lhp

The p-aminobenzamidine active site inhibited catalytic domain of murine urokinase-type plasminogen activator in complex with the allosteric inhibitory nanobody Nb7

spinqualitylabelsall models 5lhp, resolution 2.63Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lhp is a 2 chain structure with sequence from Mus musculus 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 2.63Å Ligands: EDO, PBZ, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UROK_MOUSE Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. Publication Abstract from PubMed Although trypsin-like serine proteases have flexible surface-exposed loops and are known to adopt higher and lower activity conformations, structural determinants for the different conformations have remained largely obscure. The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis. We solved five X-ray crystal structures of murine uPA (muPA) in the absence and presence of allosteric molecules and/or substrate-like molecules. The structure of unbound muPA revealed an unsuspected non-chymotrypsin-like protease conformation in which two beta-strands in the core of the protease domain undergoes a major antiparallel-to-parallel conformational transition. We next isolated two anti-muPA nanobodies; an active-site binding nanobody and an allosteric nanobody. Crystal structures of the muPA:nanobody complexes and hydrogen-deuterium exchange mass spectrometry revealed molecular insights about molecular factors controlling the antiparallel-to-parallel equilibrium in muPA. Together with muPA activity assays, the data provide valuable insights into regulatory mechanisms and conformational flexibility of uPA and trypsin-like serine proteases in general. Discovery of a novel conformational equilibrium in urokinase-type plasminogen activator.,Kromann-Hansen T, Louise Lange E, Peter Sorensen H, Hassanzadeh-Ghassabeh G, Huang M, Jensen JK, Muyldermans S, Declerck PJ, Komives EA, Andreasen PA Sci Rep. 2017 Jun 13;7(1):3385. doi: 10.1038/s41598-017-03457-7. PMID:28611361 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures Plasminogen activator Urokinase 3D Structures 3D structures of non-human antibody

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