2g1q

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[[Image:2g1q.gif|left|200px]]
[[Image:2g1q.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2g1q |SIZE=350|CAPTION= <scene name='initialview01'>2g1q</scene>, resolution 2.51&Aring;
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The line below this paragraph, containing "STRUCTURE_2g1q", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N9H:(5S)-5-(3-AMINOPROPYL)-3-(2,5-DIFLUOROPHENYL)-N-ETHYL-5-PHENYL-4,5-DIHYDRO-1H-PYRAZOLE-1-CARBOXAMIDE'>N9H</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE= KIF11, EG5, KNSL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_2g1q| PDB=2g1q | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g1q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g1q OCA], [http://www.ebi.ac.uk/pdbsum/2g1q PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g1q RCSB]</span>
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}}
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'''crystal structure of KSP in complex with inhibitor 9h'''
'''crystal structure of KSP in complex with inhibitor 9h'''
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Yan, Y.]]
[[Category: Yan, Y.]]
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[[Category: ksp]]
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[[Category: Ksp]]
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[[Category: ksp-inhibitor complex]]
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[[Category: Ksp-inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:35:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:10:43 2008''
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Revision as of 01:35, 4 May 2008

Image:2g1q.gif

Template:STRUCTURE 2g1q

crystal structure of KSP in complex with inhibitor 9h


Overview

Molecular modeling in combination with X-ray crystallographic information was employed to identify a region of the kinesin spindle protein (KSP) binding site not fully utilized by our first generation inhibitors. We discovered that by appending a propylamine substituent at the C5 carbon of a dihydropyrazole core, we could effectively fill this unoccupied region of space and engage in a hydrogen-bonding interaction with the enzyme backbone. This change led to a second generation compound with increased potency, a 400-fold enhancement in aqueous solubility at pH 4, and improved dog pharmacokinetics relative to the first generation compound.

About this Structure

2G1Q is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP., Cox CD, Torrent M, Breslin MJ, Mariano BJ, Whitman DB, Coleman PJ, Buser CA, Walsh ES, Hamilton K, Schaber MD, Lobell RB, Tao W, South VJ, Kohl NE, Yan Y, Kuo LC, Prueksaritanont T, Slaughter DE, Li C, Mahan E, Lu B, Hartman GD, Bioorg Med Chem Lett. 2006 Jun 15;16(12):3175-9. Epub 2006 Apr 5. PMID:16603356 Page seeded by OCA on Sun May 4 04:35:52 2008

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