BimC kinesins

The five remaining compounds were specifically acting on the mitotic spindle, and did not alter its components in interphase cells. One of them in particular prevented the formation of the spindle in most mitotic cells, replacing it with a monoastral microtubule formation surrounded by chromosomes the compound (9.6, Fig. 9.3) was thus named monastrol. The authors compared monastrol effects with several published effects (21-23) related to inhibition of Eg5, a member of the BimC kinesin family, and showed monastrol to be the a selective Eg5 inhibitor (Eg5-driven microtubule motility inhibition =14 pM). This compound is both the first permeable and selective inhibitor of a specific kinesin, and may have many possible applications as a tool or as the starting point for a chemical optimization program. 

The motor domain of human Eg5 (HsKSP), a member of the kinesin-5 (formerly BimC) family, shares more than 40% identity with the kinesin-1 motor domain. The overall structure of an HsKSP construct of the first 368 amino acids (including 10 amino acids of the class-specific neck linker) complexed with ADP is very similar to the structure of kinesin-1 (PDB code 1116 Turner et al., 2001). The major differences are (1) an extension of the /Miairpin / lb-L2-/ lc in the N-terminal lobe ( L2 finger ) due to an insert of eight amino acids, (2) an enlargement of loop L5 between a2a and a2b by another insert of eight amino acids, (3) an elongation of loop L10 between / 6 and [17 at the tip of the core domain, and, most remarkably,... 

Mitotic motors Kinesin BimC (bipolar) Spindle and astral MTs (+)... 

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