4DVB
The crystal structure of the Fab fragment of pro-uPA antibody mAb-112
Summary for 4DVB
| Entry DOI | 10.2210/pdb4dvb/pdb |
| Related | 2BRR 2R4R 4DW2 |
| Descriptor | Fab fragment of pro-uPA antibody mAb-112, SULFATE ION, TETRAETHYLENE GLYCOL, ... (5 entities in total) |
| Functional Keywords | immune system, hydrolase |
| Biological source | Mus musculus More |
| Total number of polymer chains | 4 |
| Total formula weight | 94074.44 |
| Authors | Jiang, L.,Botkjaer, K.A.,Andersen, L.M.,Yuan, C.,Andreasen, P.A.,Huang, M. (deposition date: 2012-02-23, release date: 2013-01-16) |
| Primary citation | Jiang, L.,Botkjaer, K.A.,Andersen, L.M.,Yuan, C.,Andreasen, P.A.,Huang, M. Rezymogenation of active urokinase induced by an inhibitory antibody. Biochem.J., 449:161-166, 2013 Cited by PubMed Abstract: 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. PubMed: 23016918DOI: 10.1042/BJ20121132 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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