1f92: Difference between revisions
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|PDB= 1f92 |SIZE=350|CAPTION= <scene name='initialview01'>1f92</scene>, resolution 2.6Å | |PDB= 1f92 |SIZE=350|CAPTION= <scene name='initialview01'>1f92</scene>, resolution 2.6Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UKP:[2,4,6-TRIISOPROPYL-PHENYLSULFONYL-L-[3-AMIDINO-PHENYLALANINYL]]-N'-BETA-ALANINYL-PIPERAZINE'>UKP</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]], [[1f5k|1F5K]], [[1f5l|1F5L]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f92 OCA], [http://www.ebi.ac.uk/pdbsum/1f92 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f92 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sturzebecher, J.]] | [[Category: Sturzebecher, J.]] | ||
[[Category: Zeslawska, E.]] | [[Category: Zeslawska, E.]] | ||
[[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 Sun Mar | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:18:14 2008'' | ||
