2Q2Z

Crystal Structure of KSP in Complex with Inhibitor 22


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP.

Roecker, A.J.Coleman, P.J.Mercer, S.P.Schreier, J.D.Buser, C.A.Walsh, E.S.Hamilton, K.Lobell, R.B.Tao, W.Diehl, R.E.South, V.J.Davide, J.P.Kohl, N.E.Yan, Y.Kuo, L.C.Li, C.Fernandez-Metzler, C.Mahan, E.A.Prueksaritanont, T.Hartman, G.D.

(2007) Bioorg Med Chem Lett 17: 5677-5682

  • DOI: https://doi.org/10.1016/j.bmcl.2007.07.074
  • Primary Citation of Related Structures:  
    2Q2Y, 2Q2Z

  • PubMed Abstract: 

    Inspired by previous efforts in the pyrazolobenzoxazine class of KSP inhibitors, the design and synthesis of 1,4-diaryl-4,5-dihydropyrazole inhibitors of KSP are described. Crystallographic evidence of binding mode and in vivo potency data is also highlighted.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Kinesin-like protein KIF11
A, B
367Homo sapiensMutation(s): 0 
Gene Names: KIF11EG5KNSL1TRIP5
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
MKK
Query on MKK

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B]
1-[(4R)-4-[3-(4-ACETYLPIPERAZIN-1-YL)PROPYL]-1-(2-FLUORO-5-METHYLPHENYL)-4-PHENYL-4,5-DIHYDRO-1H-PYRAZOL-3-YL]ETHANONE
C27 H33 F N4 O2
RYUBEOMELHCHMO-MHZLTWQESA-N
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
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
MKK PDBBind:  2Q2Z IC50: 2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.194 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.2α = 90
b = 79.45β = 90
c = 160.57γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
CrystalCleardata collection
d*TREKdata reduction
d*TREKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2007-09-18 
  • Deposition Author(s): Yan, Y.

Revision History  (Full details and data files)

  • Version 1.0: 2007-09-18
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations