Title of article :
Inhibition of a Mitotic Motor Protein: Where, How, and Conformational Consequences
Author/Authors :
Youwei Yan، نويسنده , , Vinod Sardana، نويسنده , , Bei Xu، نويسنده , , Carl Homnick، نويسنده , , Wasyl Halczenko، نويسنده , , Carolyn A. Buser، نويسنده , , Michael Schaber، نويسنده , , George D. Hartman، نويسنده , , Hans E. Huber، نويسنده , , Lawrence C. Kuo، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2004
Abstract :
We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9 Å resolution structure of the motor domain of KSP, bound with the small molecule monastrol and Mg2+·ADP, reveals that monastrol confers inhibition by “induced-fitting” onto the protein some 12 Å 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.
Keywords :
kinesin , mitotic arrest , induced-fit , X-ray structure , allosteric inhibition
Journal title :
Journal of Molecular Biology
Journal title :
Journal of Molecular Biology