1Q0B

Crystal structure of the motor protein KSP in complex with ADP and monastrol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Inhibition of a mitotic motor protein: where, how, and conformational consequences

Yan, Y.Sardana, V.Xu, B.Homnick, C.Halczenko, W.Buser, C.A.Schaber, M.Hartman, G.D.Huber, H.E.Kuo, L.C.

(2004) J Mol Biol 335: 547-554

  • DOI: https://doi.org/10.1016/j.jmb.2003.10.074
  • Primary Citation of Related Structures:  
    1Q0B

  • PubMed Abstract: 

    We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9 A resolution structure of the motor domain of KSP, bound with the small molecule monastrol and Mg2+ x ADP, reveals that monastrol confers inhibition by "induced-fitting" onto the protein some 12 A away from the catalytic center of the enzyme, resulting in the creation of a previously non-existing binding pocket. The structure provides new insights into the biochemical and mechanical mechanisms of the mitotic motor domain. Inhibition of KSP provides a novel mechanism to arrest mitotic spindle formation, a target of several approved and investigative anti-cancer agents. The structural information gleaned from this novel pocket offers a new angle for the design of anti-mitotic agents.


  • Organizational Affiliation

    Merck Research Laboratories, West Point, PA 19486, USA.


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: KIF11 OR KNSL1 OR EG5
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
NAT
Query on NAT

Download Ideal Coordinates CCD File 
E [auth A],
H [auth B]
ETHYL 4-(3-HYDROXYPHENYL)-6-METHYL-2-THIOXO-1,2,3,4-TETRAHYDROPYRIMIDINE-5-CARBOXYLATE
C14 H16 N2 O3 S
LOBCDGHHHHGHFA-LBPRGKRZSA-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
NAT PDBBind:  1Q0B IC50: 6700 (nM) from 1 assay(s)
BindingDB:  1Q0B IC50: min: 1.00e+4, max: 2.07e+4 (nM) from 2 assay(s)
Binding MOAD:  1Q0B IC50: 6700 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.220 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.3α = 90
b = 79.5β = 90
c = 159.2γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-01-13
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-16
    Changes: Data collection, Database references, Derived calculations, Refinement description