1F5L

UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-AMILORIDE COMPLEX

Summary for 1F5L

• Entry DOI: 10.2210/pdb1f5l/pdb
• Related: 1EJN 1F5K 1F92
• Descriptor: UROKINASE-TYPE PLASMINOGEN ACTIVATOR, SULFATE ION, 3,5-DIAMINO-N-(AMINOIMINOMETHYL)-6-CHLOROPYRAZINECARBOXAMIDE, ... (4 entities in total)
• Functional Keywords: urokinase, inhibitor, serine protease, human, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00749
• Total number of polymer chains: 1
• Total formula weight: 28866.10

Authors

Zeslawska, E.,Schweinitz, A.,Karcher, A.,Sondermann, P.,Sperl, S.,Sturzebecher, J.,Jacob, U. (deposition date: 2000-06-15, release date: 2001-06-15, Last modification date: 2024-11-13)

Primary citation

Zeslawska, E.,Schweinitz, A.,Karcher, A.,Sondermann, P.,Sperl, S.,Sturzebecher, J.,Jacob, U.
Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design.
J.Mol.Biol., 301:465-475, 2000

PubMed Abstract: Urokinase is a serine protease involved in cancer growth and metastasis. Here we present the first urokinase crystal structure in complex with reversible inhibitors at 2.1 and 2.6 A resolution. These inhibitor complex structures have been obtained from crystals of engineered urokinase type plasminogen activator designed to obtain a crystal form open for inhibitor soaking. The mutant C122S loses its flexible A-chain upon activation cleavage and crystallizes in the presence of benzamidine, which was later displaced by the desired inhibitor. This new soakable crystal form turned out to be of great value in the process of structure-based drug design. The evaluated binding mode of amiloride, and UKI-1D revealed a new subsite of the primary specificity pocket of urokinase that will be employed in the future ligand optimisation process.

PubMed: 10926521
DOI: 10.1006/jmbi.2000.3966

Experimental method

X-RAY DIFFRACTION (2.1 Å)