4dvb

The crystal structure of the Fab fragment of pro-uPA antibody mAb-112

spinqualitylabelsall models 4dvb, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4dvb 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. Ligands: PG4, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed An important regulatory mechanism of serine proteases is the proteolytic conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This activation process is generally considered an irreversible process. In the present study, we demonstrate that an active enzyme can be converted back into its zymogen form. We determined the crystal structure of uPA (urokinase-type plasminogen activator) in complex with an inhibitory antibody, revealing that the antibody 'rezymogenizes' already activated uPA. The present study demonstrates a new regulatory mechanism of protease activity, which is also an extreme case of protein allostery. Mechanistically, the antibody binds a single surface-exposed loop, named the autolysis loop, thereby preventing the stabilization of uPA in its active conformation. We argue that this autolysis loop is a key structural element for rezymogenation of other proteases, and will be a new target site for pharmacological intervention with serine protease activity. Rezymogenation of active urokinase induced by an inhibitory antibody.,Jiang L, Botkjaer KA, Andersen LM, Yuan C, Andreasen PA, Huang M Biochem J. 2013 Jan 1;449(1):161-6. doi: 10.1042/BJ20121132. PMID:23016918 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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