1Q0B

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

Summary for 1Q0B

• Entry DOI: 10.2210/pdb1q0b/pdb
• Descriptor: Kinesin-like protein KIF11, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: cell cycle, motor protein, monastrol
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P52732
• Total number of polymer chains: 2
• Total formula weight: 83336.49

Authors

Yan, Y.,Sardana, V.,Xu, B.,Halczenko, W.,Homnick, C.,Buser, C.A.,Hartman, G.D.,Huber, H.E.,Kuo, L.C. (deposition date: 2003-07-15, release date: 2004-01-13, Last modification date: 2023-08-16)

Primary citation

Yan, Y.,Sardana, V.,Xu, B.,Homnick, C.,Halczenko, W.,Buser, C.A.,Schaber, M.,Hartman, G.D.,Huber, H.E.,Kuo, L.C.
Inhibition of a mitotic motor protein: where, how, and conformational consequences
J.Mol.Biol., 335:547-554, 2004

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.

PubMed: 14672662
DOI: 10.1016/j.jmb.2003.10.074

Experimental method

X-RAY DIFFRACTION (1.9 Å)