3QN7

Potent and selective bicyclic peptide inhibitor (UK18) of human urokinase-type plasminogen activator(uPA)

Summary for 3QN7

• Entry DOI: 10.2210/pdb3qn7/pdb
• Related: 1LMW 2NWN
• Descriptor: Urokinase-type plasminogen activator, Bicyclic peptide inhibitor, 1,3,5-tris(bromomethyl)benzene, ... (4 entities in total)
• Functional Keywords: bicyclic peptide inhibitor, chymotrypsin fold, serine protease, urokinase receptor (upar), extracellular, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00749
• Total number of polymer chains: 2
• Total formula weight: 30592.25

Authors

Angelini, A.,Cendron, L.,Touati, J.,Winter, G.,Zanotti, G.,Heinis, C. (deposition date: 2011-02-08, release date: 2012-02-15, Last modification date: 2024-11-13)

Primary citation

Angelini, A.,Cendron, L.,Chen, S.,Touati, J.,Winter, G.,Zanotti, G.,Heinis, C.
Bicyclic peptide inhibitor reveals large contact interface with a protease target
Acs Chem.Biol., 7:817-821, 2012

PubMed Abstract: From a large combinatorial library of chemically constrained bicyclic peptides we isolated a selective and potent (K(i) = 53 nM) inhibitor of human urokinase-type plasminogen activator (uPA) and crystallized the complex. This revealed an extended structure of the peptide with both peptide loops engaging the target to form a large interaction surface of 701 Å(2) with multiple hydrogen bonds and complementary charge interactions, explaining the high affinity and specificity of the inhibitor. The interface resembles that between two proteins and suggests that these constrained peptides have the potential to act as small protein mimics.

PubMed: 22304751
DOI: 10.1021/cb200478t

Experimental method

X-RAY DIFFRACTION (1.9 Å)