2vip
From Proteopedia
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|PDB= 2vip |SIZE=350|CAPTION= <scene name='initialview01'>2vip</scene>, resolution 1.72Å | |PDB= 2vip |SIZE=350|CAPTION= <scene name='initialview01'>2vip</scene>, resolution 1.72Å | ||
|SITE= <scene name='pdbsite=AC1:Act+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+A'>AC2</scene> and <scene name='pdbsite=AC3:L1r+Binding+Site+For+Chain+A'>AC3</scene> | |SITE= <scene name='pdbsite=AC1:Act+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+A'>AC2</scene> and <scene name='pdbsite=AC3:L1r+Binding+Site+For+Chain+A'>AC3</scene> | ||
| - | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=L1R:4-(2-AMINOETHOXY)-3,5-DICHLORO-N-[3-(1-METHYLETHOXY)PHENYL]BENZAMIDE'>L1R</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=[[2viv|2VIV]], [[1c5x|1C5X]], [[1gj9|1GJ9]], [[2vio|2VIO]], [[1w0z|1W0Z]], [[1fv9|1FV9]], [[1vja|1VJA]], [[1gj8|1GJ8]], [[1w11|1W11]], [[1sqo|1SQO]], [[1gjd|1GJD]], [[1w10|1W10]], [[1owk|1OWK]], [[1w12|1W12]], [[1gi9|1GI9]], [[1o5a|1O5A]], [[1c5z|1C5Z]], [[1owj|1OWJ]], [[1gi7|1GI7]], [[1o5b|1O5B]], [[1gjc|1GJC]], [[1sc8|1SC8]], [[1gja|1GJA]], [[1o3p|1O3P]], [[1owe|1OWE]], [[1sqa|1SQA]], [[1gjb|1GJB]], [[2viw|2VIW]], [[1f92|1F92]], [[1owi|1OWI]], [[1kdu|1KDU]], [[2vin|2VIN]], [[1sqt|1SQT]], [[1f5l|1F5L]], [[1owd|1OWD]], [[1ejn|1EJN]], [[2viq|2VIQ]], [[1lmw|1LMW]], [[1u6q|1U6Q]], [[1gi8|1GI8]], [[2jde|2JDE]], [[1c5y|1C5Y]], [[1w14|1W14]], [[1vj9|1VJ9]], [[1w13|1W13]], [[1gj7|1GJ7]], [[1c5w|1C5W]], [[1owh|1OWH]], [[1o5c|1O5C]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vip OCA], [http://www.ebi.ac.uk/pdbsum/2vip PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vip RCSB]</span> | ||
}} | }} | ||
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[[Category: Vinkovic, M.]] | [[Category: Vinkovic, M.]] | ||
[[Category: Wallis, N G.]] | [[Category: Wallis, N G.]] | ||
| - | [[Category: ACT]] | ||
| - | [[Category: L1R]] | ||
| - | [[Category: SO4]] | ||
[[Category: blood coagulation]] | [[Category: blood coagulation]] | ||
[[Category: egf-like domain]] | [[Category: egf-like domain]] | ||
| Line 53: | Line 53: | ||
[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:12:47 2008'' |
Revision as of 02:12, 31 March 2008
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| , resolution 1.72Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , and | ||||||
| Ligands: | , , | ||||||
| Activity: | U-plasminogen activator, with EC number 3.4.21.73 | ||||||
| Related: | 2VIV, 1C5X, 1GJ9, 2VIO, 1W0Z, 1FV9, 1VJA, 1GJ8, 1W11, 1SQO, 1GJD, 1W10, 1OWK, 1W12, 1GI9, 1O5A, 1C5Z, 1OWJ, 1GI7, 1O5B, 1GJC, 1SC8, 1GJA, 1O3P, 1OWE, 1SQA, 1GJB, 2VIW, 1F92, 1OWI, 1KDU, 2VIN, 1SQT, 1F5L, 1OWD, 1EJN, 2VIQ, 1LMW, 1U6Q, 1GI8, 2JDE, 1C5Y, 1W14, 1VJ9, 1W13, 1GJ7, 1C5W, 1OWH, 1O5C
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
FRAGMENT-BASED DISCOVERY OF MEXILETINE DERIVATIVES AS ORALLY BIOAVAILABLE INHIBITORS OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR
Overview
Fragment-based lead discovery has been applied to urokinase-type plasminogen activator (uPA). The (R)-enantiomer of the orally active drug mexiletine 5 (a fragment hit from X-ray crystallographic screening) was the chemical starting point. Structure-aided design led to elaborated inhibitors that retained the key interactions of (R)-5 while gaining extra potency by simultaneously occupying neighboring regions of the active site. Subsequent optimization led to 15, a potent, selective, and orally bioavailable inhibitor of uPA.
About this Structure
2VIP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator., Frederickson M, Callaghan O, Chessari G, Congreve M, Cowan SR, Matthews JE, McMenamin R, Smith DM, Vinkovic M, Wallis NG, J Med Chem. 2008 Jan 24;51(2):183-6. Epub 2007 Dec 29. PMID:18163548
Page seeded by OCA on Mon Mar 31 05:12:47 2008
Categories: Homo sapiens | Single protein | U-plasminogen activator | Callaghan, O. | Chessari, G. | Congreve, M. | Cowan, S R. | Frederickson, M. | Matthews, J E. | Mcmenamin, R. | Smith, D. | Vinkovic, M. | Wallis, N G. | Blood coagulation | Egf-like domain | Fibrinolysis | Glycoprotein | Hydrolase | Inhibitor | Kringle | Pharmaceutical | Phosphorylation | Plasminogen activation | Polymorphism | Protease | Secreted | Serine protease | Urokinase-type plasminogen activator | Zymogen
