"Snapshots" of ispinesib-induced conformational changes in the mitotic kinesin Eg5.

ABSTRACT: Kinesins comprise a superfamily of molecular motors that drive a wide variety of cellular physiologies, from cytoplasmic transport to formation of the bipolar spindle in mitosis. These differing roles are reflected in corresponding polymorphisms in key kinesin structural elements. One of these is a unique loop and stem motif found in all kinesins and referred to as loop 5 (L5). This loop is longest in the mitotic kinesin Eg5 and is the target for a number of small molecule inhibitors, including ispinesib, which is being used in clinical trials in patients with cancer. In this study, we have used x-ray crystallography to identify a new structure of an Eg5-ispinesib complex and have combined this with transient state kinetics to identify a plausible sequence of conformational changes that oc

SUBMITTER: Kaan HY 

PROVIDER: S-EPMC3689998 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature