2fme
From Proteopedia
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| - | [[Image:2fme.gif|left|200px]] | + | [[Image:2fme.gif|left|200px]] |
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| - | '''Crystal structure of the mitotic kinesin eg5 (ksp) in complex with mg-adp and (r)-4-(3-hydroxyphenyl)-n,n,7,8-tetramethyl-3,4-dihydroisoquinoline-2(1h)-carboxamide''' | + | {{Structure |
| + | |PDB= 2fme |SIZE=350|CAPTION= <scene name='initialview01'>2fme</scene>, resolution 2.10Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=3QC:(4R)-4-(3-HYDROXYPHENYL)-N,N,7,8-TETRAMETHYL-3,4-DIHYDROISOQUINOLINE-2(1H)-CARBOXAMIDE'>3QC</scene> and <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= KIF11, EG5, KNSL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of the mitotic kinesin eg5 (ksp) in complex with mg-adp and (r)-4-(3-hydroxyphenyl)-n,n,7,8-tetramethyl-3,4-dihydroisoquinoline-2(1h)-carboxamide''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2FME is a [ | + | 2FME is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FME OCA]. |
==Reference== | ==Reference== | ||
| - | Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl-tetrahydroisoquinoline lead series., Tarby CM, Kaltenbach RF 3rd, Huynh T, Pudzianowski A, Shen H, Ortega-Nanos M, Sheriff S, Newitt JA, McDonnell PA, Burford N, Fairchild CR, Vaccaro W, Chen Z, Borzilleri RM, Naglich J, Lombardo LJ, Gottardis M, Trainor GL, Roussell DL, Bioorg Med Chem Lett. 2006 Apr 15;16(8):2095-100. Epub 2006 Feb 3. PMID:[http:// | + | Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl-tetrahydroisoquinoline lead series., Tarby CM, Kaltenbach RF 3rd, Huynh T, Pudzianowski A, Shen H, Ortega-Nanos M, Sheriff S, Newitt JA, McDonnell PA, Burford N, Fairchild CR, Vaccaro W, Chen Z, Borzilleri RM, Naglich J, Lombardo LJ, Gottardis M, Trainor GL, Roussell DL, Bioorg Med Chem Lett. 2006 Apr 15;16(8):2095-100. Epub 2006 Feb 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16458511 16458511] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: eg5 ksp mg-adp complex inhibitor]] | [[Category: eg5 ksp mg-adp complex inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:54:14 2008'' |
Revision as of 14:54, 20 March 2008
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| , resolution 2.10Å | |||||||
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| Ligands: | , and | ||||||
| Gene: | KIF11, EG5, KNSL1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the mitotic kinesin eg5 (ksp) in complex with mg-adp and (r)-4-(3-hydroxyphenyl)-n,n,7,8-tetramethyl-3,4-dihydroisoquinoline-2(1h)-carboxamide
Overview
In a high-throughput screening effort, a series of tetrahydroisoquinolines was identified as modest inhibitors of human Eg5. A medicinal chemistry optimization effort led to the identification of R-4-(3-hydroxyphenyl)-N,N-7,8-tetramethyl-3,4-dihydroisoquinoline-2(1H)-ca rboxamide (32a) as a potent inhibitor of human Eg5 (ATPase IC50 104 nM) with good anti-proliferative activity in A2780 cells (IC50 234 nM).
About this Structure
2FME is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl-tetrahydroisoquinoline lead series., Tarby CM, Kaltenbach RF 3rd, Huynh T, Pudzianowski A, Shen H, Ortega-Nanos M, Sheriff S, Newitt JA, McDonnell PA, Burford N, Fairchild CR, Vaccaro W, Chen Z, Borzilleri RM, Naglich J, Lombardo LJ, Gottardis M, Trainor GL, Roussell DL, Bioorg Med Chem Lett. 2006 Apr 15;16(8):2095-100. Epub 2006 Feb 3. PMID:16458511
Page seeded by OCA on Thu Mar 20 16:54:14 2008
