{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:47:34Z","timestamp":1791827254591,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T00:00:00Z","timestamp":1390780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2014,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Laulimalide and peloruside\u2005A are microtubule\u2010stabilizing agents (MSAs), the mechanism of action on microtubules of which is poorly defined. Here, using X\u2010ray crystallography it is shown that laulimalide and peloruside\u2005A bind to a unique non\u2010taxane site on \u03b2\u2010tubulin and use their respective macrolide core structures to interact with a second tubulin dimer across protofilaments. At the same time, they allosterically stabilize the taxane\u2010site M\u2010loop that establishes lateral tubulin contacts in microtubules. Structures of ternary complexes of tubulin with laulimalide\/peloruside\u2005A and epothilone\u2005A are also solved, and a crosstalk between the laulimalide\/peloruside and taxane sites via the M\u2010loop of \u03b2\u2010tubulin is found. Together, the data define the mechanism of action of laulimalide and peloruside\u2005A on tubulin and microtubules. The data further provide a structural framework for understanding the synergy observed between two classes of MSAs in tubulin assembly and the inhibition of cancer cell growth.<\/jats:p>","DOI":"10.1002\/anie.201307749","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T21:08:28Z","timestamp":1390856908000},"page":"1621-1625","source":"Crossref","is-referenced-by-count":196,"title":["Structural Basis of Microtubule Stabilization by Laulimalide and Peloruside\u2005A"],"prefix":"10.1002","volume":"53","author":[{"given":"Andrea E.","family":"Prota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Bargsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Northcote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2010Heinz","family":"Altmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Fernando","family":"D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel O.","family":"Steinmetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,27]]},"reference":[{"key":"e_1_2_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3253"},{"key":"e_1_2_2_2_2","first-page":"653","volume":"59","author":"Mooberry S. 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