3laq

Structure-based engineering of species selectivity in the uPA-uPAR interactionStructure-based engineering of species selectivity in the uPA-uPAR interaction

Structural highlights 3laq is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UROK_MOUSE Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) is decisive for cell surface-associated plasminogen activation. Because plasmin activity controls fibrinolysis in a variety of pathological conditions, including cancer and wound healing, several intervention studies have focused on targeting the uPA.uPAR interaction in vivo. Evaluations of such studies in xenotransplanted tumor models are, however, complicated by the pronounced species selectivity in this interaction. We now report the molecular basis underlying this difference by solving the crystal structure for the murine uPA.uPAR complex and demonstrate by extensive surface plasmon resonance studies that the kinetic rate constants for this interaction can be swapped completely between these orthologs by exchanging only two residues. This study not only discloses the structural basis required for a successful rational design of the species selectivity in the uPA.uPAR interaction, which is highly relevant for functional studies in mouse models, but it also suggests the possible development of general inhibitors that will target the uPA.uPAR interaction across species barriers. Structure-based engineering of species selectivity in the interaction between urokinase and its receptor: implication for preclinical cancer therapy.,Lin L, Gardsvoll H, Huai Q, Huang M, Ploug M J Biol Chem. 2010 Apr 2;285(14):10982-92. Epub 2010 Feb 4. PMID:20133942 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Urokinase 3D Structures Urokinase plasminogen activator surface receptor 3D structures

spinqualitylabelsall models 3laq, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image