1f5k
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Urokinase is a serine protease involved in cancer growth and metastasis. | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: urokinase]] | [[Category: urokinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:35:05 2008'' |
Revision as of 10:35, 21 February 2008
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UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-BENZAMIDINE COMPLEX
Contents |
Overview
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.
Disease
Known disease associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[191840]
About this Structure
1F5K is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as U-plasminogen activator, with EC number 3.4.21.73 Full crystallographic information is available from OCA.
Reference
Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design., Zeslawska E, Schweinitz A, Karcher A, Sondermann P, Sperl S, Sturzebecher J, Jacob U, J Mol Biol. 2000 Aug 11;301(2):465-75. PMID:10926521
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