1f5k
From Proteopedia
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|PDB= 1f5k |SIZE=350|CAPTION= <scene name='initialview01'>1f5k</scene>, resolution 1.8Å | |PDB= 1f5k |SIZE=350|CAPTION= <scene name='initialview01'>1f5k</scene>, resolution 1.8Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=BAM:BENZAMIDINE'>BAM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1ejn|1EJN]], [[1f5l|1F5L]], [[1f92|1F92]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f5k OCA], [http://www.ebi.ac.uk/pdbsum/1f5k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f5k RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191840 191840]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sturzebecher, J.]] | [[Category: Sturzebecher, J.]] | ||
[[Category: Zeslawska, E.]] | [[Category: Zeslawska, E.]] | ||
| - | [[Category: BAM]] | ||
| - | [[Category: SO4]] | ||
[[Category: human]] | [[Category: human]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
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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 Sun Mar 30 20:16:17 2008'' |
Revision as of 17:16, 30 March 2008
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| , resolution 1.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | U-plasminogen activator, with EC number 3.4.21.73 | ||||||
| Related: | 1EJN, 1F5L, 1F92
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-BENZAMIDINE COMPLEX
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.
About this Structure
1F5K is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 20:16:17 2008
