1yrs

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File:1yrs.jpg


1yrs, resolution 2.5Å

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Crystal structure of KSP in complex with inhibitor 1

OverviewOverview

Optimization of high-throughput screening (HTS) hits resulted in the discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of KSP. Dihydropyrazole 15 is a potent, cell-active KSP inhibitor that induces apoptosis and generates aberrant mitotic spindles in human ovarian carcinoma cells at low nanomolar concentrations. X-ray crystallographic evidence is presented which demonstrates that these inhibitors bind in an allosteric pocket of KSP distant from the nucleotide and microtubule binding sites.

About this StructureAbout this Structure

1YRS is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Kinesin spindle protein (KSP) inhibitors. Part 1: The discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of the mitotic kinesin KSP., Cox CD, Breslin MJ, Mariano BJ, Coleman PJ, Buser CA, Walsh ES, Hamilton K, Huber HE, Kohl NE, Torrent M, Yan Y, Kuo LC, Hartman GD, Bioorg Med Chem Lett. 2005 Apr 15;15(8):2041-5. PMID:15808464

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