1YRS

Crystal structure of KSP in complex with inhibitor 1

Summary for 1YRS

• Entry DOI: 10.2210/pdb1yrs/pdb
• Descriptor: Kinesin-like protein KIF11, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P52732
• Total number of polymer chains: 2
• Total formula weight: 83643.71

Authors

Cox, C.D.,Breslin, M.J.,Mariano, B.J.,Coleman, P.J.,Buser, C.A.,Walsh, E.S.,Hamilton, K.,Kohl, N.E.,Torrent, M.,Yan, Y.,Kuo, L.C.,Hartman, G.D. (deposition date: 2005-02-04, release date: 2005-04-12, Last modification date: 2023-08-23)

Primary citation

Cox, C.D.,Breslin, M.J.,Mariano, B.J.,Coleman, P.J.,Buser, C.A.,Walsh, E.S.,Hamilton, K.,Huber, H.E.,Kohl, N.E.,Torrent, M.,Yan, Y.,Kuo, L.C.,Hartman, G.D.
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
BIOORG.MED.CHEM.LETT., 15:2041-2045, 2005

PubMed Abstract: 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.

PubMed: 15808464
DOI: 10.1016/j.bmcl.2005.02.055

Experimental method

X-RAY DIFFRACTION (2.5 Å)