3wpn
From Proteopedia
(Difference between revisions)
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref> | [[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Kinesin spindle protein Eg5 is a target for anticancer therapies, and small molecule inhibitors of its ATPase activity have been developed. We herein report for the first time the crystal structure of and biochemical studies on the Eg5 motor domain in complex with a new type of allosteric inhibitor. The biphenyl-type inhibitor PVZB1194 binds to the alpha4/alpha6 allosteric pocket 15 A from the ATP-binding pocket, which differs from conventional allosteric inhibitors that bind to the allosteric L5/alpha2/alpha3 pocket of Eg5. Binding of the inhibitor is involved in the neck-linker conformation and also causes conformational changes around the ATP-binding pocket through Tyr104 to affect the interaction of ATP with the pocket. This structure provides useful information for the development of novel types of allosteric drugs as well as a novel insight into the molecular mechanism responsible for regulating the motor activity of kinesins. | ||
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| + | Structural basis of new allosteric inhibition in Kinesin spindle protein eg5.,Yokoyama H, Sawada J, Katoh S, Matsuno K, Ogo N, Ishikawa Y, Hashimoto H, Fujii S, Asai A ACS Chem Biol. 2015 Apr 17;10(4):1128-36. doi: 10.1021/cb500939x. Epub 2015 Feb, 3. PMID:25622007<ref>PMID:25622007</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 05:33, 30 April 2015
Kinesin spindle protein Eg5 in complex with ATP-competitive inhibitor PVZB1194
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