1YRS

Crystal structure of KSP in complex with inhibitor 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.310 
  • R-Value Work: 0.250 
  • R-Value Observed: 0.250 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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, 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.

(2005) Bioorg Med Chem Lett 15: 2041-2045

  • DOI: https://doi.org/10.1016/j.bmcl.2005.02.055
  • Primary Citation of Related Structures:  
    1YRS

  • 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.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, Sumneytown Pike, West Point, PA 19486, USA. chris_cox@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Kinesin-like protein KIF11
A, B
368Homo sapiensMutation(s): 0 
Gene Names: KIF11EG5KNSL1
UniProt & NIH Common Fund Data Resources
Find proteins for P52732 (Homo sapiens)
Explore P52732 
Go to UniProtKB:  P52732
PHAROS:  P52732
GTEx:  ENSG00000138160 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP52732
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADP
Query on ADP

Download Ideal Coordinates CCD File 
D [auth A],
G [auth B]
ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
L47
Query on L47

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B]
3-[(5S)-1-ACETYL-3-(2-CHLOROPHENYL)-4,5-DIHYDRO-1H-PYRAZOL-5-YL]PHENOL
C17 H15 Cl N2 O2
QBZAPFWYAPXRGQ-KRWDZBQOSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
L47 Binding MOAD:  1YRS IC50: 450 (nM) from 1 assay(s)
PDBBind:  1YRS IC50: 450 (nM) from 1 assay(s)
BindingDB:  1YRS IC50: 450 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.310 
  • R-Value Work: 0.250 
  • R-Value Observed: 0.250 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.3α = 90
b = 79.8β = 90
c = 159.6γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
CNSrefinement
HKL-2000data reduction
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-04-12
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description